RU2786842C1 - Agent with antibacterial activity against escherichia coli cell culture - Google Patents
Agent with antibacterial activity against escherichia coli cell culture Download PDFInfo
- Publication number
- RU2786842C1 RU2786842C1 RU2022113063A RU2022113063A RU2786842C1 RU 2786842 C1 RU2786842 C1 RU 2786842C1 RU 2022113063 A RU2022113063 A RU 2022113063A RU 2022113063 A RU2022113063 A RU 2022113063A RU 2786842 C1 RU2786842 C1 RU 2786842C1
- Authority
- RU
- Russia
- Prior art keywords
- escherichia coli
- cell culture
- antibacterial activity
- copper
- against escherichia
- Prior art date
Links
- 238000004113 cell culture Methods 0.000 title claims abstract description 6
- 230000000844 anti-bacterial effect Effects 0.000 title abstract description 17
- 241000588724 Escherichia coli Species 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 24
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims abstract description 20
- 241001646716 Escherichia coli K-12 Species 0.000 claims abstract description 8
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 4
- 230000000694 effects Effects 0.000 abstract description 7
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 2
- 230000001580 bacterial effect Effects 0.000 description 16
- 239000000243 solution Substances 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 8
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 7
- BIIKTLDVBFVWLX-UHFFFAOYSA-N 4-hydroxy-3-[(4-hydroxy-6-methyl-2-oxopyran-3-yl)-(3-nitrophenyl)methyl]-6-methylpyran-2-one Chemical compound O=C1OC(C)=CC(O)=C1C(C=1C(OC(C)=CC=1O)=O)C1=CC=CC([N+]([O-])=O)=C1 BIIKTLDVBFVWLX-UHFFFAOYSA-N 0.000 description 5
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- YKVRKCXHJIXVAU-UHFFFAOYSA-N 4-hydroxy-3-[(4-hydroxy-6-methyl-2-oxopyran-3-yl)-phenylmethyl]-6-methylpyran-2-one Chemical compound O=C1OC(C)=CC(O)=C1C(C=1C(OC(C)=CC=1O)=O)C1=CC=CC=C1 YKVRKCXHJIXVAU-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229930193140 Neomycin Natural products 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229960004927 neomycin Drugs 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 230000009036 growth inhibition Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000007725 thermal activation Methods 0.000 description 3
- RXWOHFUULDINMC-UHFFFAOYSA-N 2-(3-nitrothiophen-2-yl)acetic acid Chemical compound OC(=O)CC=1SC=CC=1[N+]([O-])=O RXWOHFUULDINMC-UHFFFAOYSA-N 0.000 description 2
- 150000000464 2H-pyran-2-ones Chemical class 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 206010029155 Nephropathy toxic Diseases 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- BFGKITSFLPAWGI-UHFFFAOYSA-N chromium(3+) Chemical compound [Cr+3] BFGKITSFLPAWGI-UHFFFAOYSA-N 0.000 description 2
- 229960003405 ciprofloxacin Drugs 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 231100000417 nephrotoxicity Toxicity 0.000 description 2
- -1 poly(acrylic acid) Polymers 0.000 description 2
- 150000007660 quinolones Chemical class 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- NSYSSMYQPLSPOD-UHFFFAOYSA-N triacetate lactone Chemical compound CC1=CC(O)=CC(=O)O1 NSYSSMYQPLSPOD-UHFFFAOYSA-N 0.000 description 2
- WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 1
- DMTRKPKZQVCOIF-QPJJXVBHSA-N 4-hydroxy-3-[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-6-methylpyran-2-one Chemical compound OC1=C(C(OC(=C1)C)=O)C(\C=C\C1=CC=C(C=C1)O)=O DMTRKPKZQVCOIF-QPJJXVBHSA-N 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 206010033109 Ototoxicity Diseases 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 231100000895 deafness Toxicity 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 231100000262 ototoxicity Toxicity 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 238000004313 potentiometry Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Natural products CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 1
- 229960002385 streptomycin sulfate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
Images
Abstract
Description
Изобретение относится к фармакологии, в частности к применению комплексных соединений меди(II) на основе арилметиленбиспиран-2-онов в качестве антимикробного препарата, а именно – в качестве средства, обладающего антибактериальной активностью в отношении культуры клеток Escherichia coli K-12 (депонирован в IBPPM 204). The invention relates to pharmacology, in particular to the use of copper(II) complex compounds based on arylmethylenebispyran-2-ones as an antimicrobial agent, namely, as an agent with antibacterial activity against Escherichia coli K-12 cell culture (deposited in IBPPM 204).
Известны соединения, проявляющие антибактериальную активность по отношению к различным видам бактериальных культур.Known compounds that exhibit antibacterial activity against various types of bacterial cultures.
Известны препараты неомицин (см. патент США №2799620, по кл. МПК С07H15/282, опубл. 16.07.1957) и ципрофлоксацин (Norry S.R. Side-effects of quinolones: comparisons between quinolones and other antibiotics // Eur. J. Clin. Microbiol. Infect. Dis.- 1991.-V. 10.- P. 378-383), а также аналог неомицина – стрептомицин (см. патент США №2799620, по кл. МПК С07H15/282, опубл. 16.07.1957). Known drugs are neomycin (see US patent No. 2799620, according to class IPC C07H15 / 282, publ. 07/16/1957) and ciprofloxacin (Norry S.R. Side-effects of quinolones: comparisons between quinolones and other antibiotics // Eur. J. Clin. Microbiol. Infect. Dis.- 1991.-V. 10.- P. 378-383), as well as an analogue of neomycin - streptomycin (see US patent No. 2799620, according to IPC class С07H15 / 282, publ. 07/16/1957) .
Недостатками неомицина (см. Youssef F.S. at al. Application of some nanoparticles in the field of veterinary medicine // Int. J. Vet. Sci. Med.- 2019.-V. 7.-N.1.- P. 78-93) и его производных (см. Nurkeeva Z.S. at al. Polycomplexes of poly(acrylic acid) with streptomycin sulfate and their antibacterial activity // Eur. J. Pharm. Biopharm.-2004. - V.57. - P. 245-249) является наличие нежелательных побочных эффектов, таких как нефротоксичность и ототоксичность, необратимая глухота, токсическая нефропатия.The disadvantages of neomycin (see Youssef F.S. at al. Application of some nanoparticles in the field of veterinary medicine // Int. J. Vet. Sci. Med.- 2019.-V. 7.-N.1.- P. 78- 93) and its derivatives (see Nurkeeva Z.S. at al. Polycomplexes of poly(acrylic acid) with streptomycin sulfate and their antibacterial activity // Eur. J. Pharm. Biopharm.-2004. - V.57. - P. 245- 249) is the presence of undesirable side effects, such as nephrotoxicity and ototoxicity, irreversible deafness, toxic nephropathy.
Известны комплексные соединения Cu(II), Ni(II), Co(II), Mn(II), Fe(III) на основе 2H-пиран-2-онов, обладающие антибактериальными свойствами в отношении грамотрицательных (E. coli) и грамположительных (S. aureus) бактерий. Наиболее высокую активность проявил комплекс меди(II), зона ингибирования которого составила 27 и 18 мм, соответственно, при минимальной ингибирующей концентрации (МИК) 0,5 мг/мл, что выше, по сравнению с лигандом - 15 и 09 мм (0,5 мг/мл), но ниже, чем у препарата сравнения – ципрофлоксацина – 40 и 42 мм (0,5 мг/мл) (см. Jadhav S.M. at al. Synthesis, characterization, potentiometry, and antimicrobial studies of transition metal complexes of a tridentate ligand // J. Coord. Chem. – 2010. – V. 63. – N. 23. - P. 4153-4164). Complex compounds of Cu(II), Ni(II), Co(II), Mn(II), Fe(III) based on 2H-pyran-2-ones are known, which have antibacterial properties against gram-negative ( E. coli ) and gram-positive ( S. aureus ) bacteria. The copper(II) complex showed the highest activity, the zone of inhibition of which was 27 and 18 mm, respectively, at a minimum inhibitory concentration (MIC) of 0.5 mg/ml, which is higher compared to the ligand - 15 and 09 mm (0. 5 mg/ml), but lower than the reference drug ciprofloxacin at 40 and 42 mm (0.5 mg/ml) (see Jadhav SM at al. Synthesis, characterization, potentiometry, and antimicrobial studies of transition metal complexes of a tridentate ligand // J. Coord Chem. - 2010. - V. 63. - N. 23. - P. 4153-4164).
лиганд M=Cu(II), Ni(II), M’=Fe(III) Co(II), Mn(II) ligand M=Cu(II), Ni(II), M'=Fe(III) Co(II), Mn(II)
В отношении грамотрицательных (E. coli) и грамположительных (S. aureus) бактерий исследована антибактериальная активность in vitro комплексов Ni(II), Cu(II), Co(II), Mn(II), Fe(III) на основе 2H-пиран-2-онов методом бумажных дисков. Комплексные соединения Ni(II), Co(II), Mn(II), Fe(III) проявили умеренную активность по сравнению с неомицином. Наиболее выраженный эффект показал комплекс Cu(II), для которого зона ингибирования составила 22 мм при МИК 1мг/мл (см. Patange V.N. at al. Synthesis, spectral, thermal and biological studies of transition metal complexes of 4-hydroxy-3-[3-(4-hydroxyphenyl)-acryloyl]-6-methyl-2H-pyran-2-one // J. Serb.Chem. Soc. – 2011. – V. 76. –N. 9. – P. 1237-1246).The in vitro antibacterial activity of Ni (II), Cu(II), Co(II), Mn(II), Fe(III) complexes based on 2H- pyran-2-ones by the paper disk method. Ni(II), Co(II), Mn(II), Fe(III) complex compounds showed moderate activity compared to neomycin. The most pronounced effect was shown by the Cu(II) complex, for which the zone of inhibition was 22 mm at MIC 1 mg/ml (see Patange VN at al. Synthesis, spectral, thermal and biological studies of transition metal complexes of 4-hydroxy-3-[ 3-(4-hydroxyphenyl)-acryloyl]-6-methyl-2 H -pyran-2-one // J. Serb.Chem. Soc. - 2011. - V. 76. - N. 9. - P. 1237 -1246).
DMF – N,N-Диметилформамид, М= Cu(II), Ni(II), Co(II), Mn(II) и X=Cl, где М= Fe(III)DMF - N,N-Dimethylformamide, M= Cu(II), Ni(II), Co(II), Mn(II) and X=Cl, where M= Fe(III)
Известны также комплексные соединения Co(II), Cr(III) и Fe(III) с формулой:Complex compounds of Co(II), Cr(III) and Fe(III) are also known with the formula:
где М=Co, X=2; M=Cr, Fe, X=4,where M=Co, X=2; M=Cr, Fe, X=4,
обладающие антибактериальными свойствами, которые были исследованы в отношении грамотрицательных (E. coli) и грамположительных (S. aureus) бактерий. Активность оценивали путем измерения зон ингибирования, наблюдаемые вокруг испытуемых соединений. Наибольшие зоны ингибирования наблюдались у комплекса Co(II) и составляли 20 и 19 мм соответственно (см. Al-Obaidi O.H. Synthesis and theoretical evaluation of new binuclear Cr(III), Co(II) and Fe(III) metal complexes of tetradentate Schiff base and its biological activity // Int. J. Biochem. Res.&Rev. – 2015. – V.5. – N.1. – P. 49-55).with antibacterial properties, which have been investigated against Gram-negative ( E. coli ) and Gram-positive ( S. aureus ) bacteria. Activity was assessed by measuring the zones of inhibition observed around the test compounds. The largest zones of inhibition were observed in the Co(II) complex and were 20 and 19 mm, respectively (see Al-Obaidi OH Synthesis and theoretical evaluation of new binuclear Cr(III), Co(II) and Fe(III) metal complexes of tetradentate Schiff base and its biological activity // Int. J. Biochem. Res.&Rev. - 2015. - V.5. - N.1. - P. 49-55).
Изобретение направлено на решение проблемы расширения арсенала средств, обладающих антибактериальным действием в отношении бактериальной суспензии Escherichia coli K-12.The invention is aimed at solving the problem of expanding the arsenal of agents with antibacterial action against a bacterial suspension of Escherichia coli K-12.
Поставленная проблема решается применением комплексов меди(II) на основе арилметиленбиспирн-2-онов формулы The problem posed is solved by using copper(II) complexes based on arylmethylenebispyrn-2-ones of the formula
где при n = 4 R=H (1) или R=3-NO2 (2)where at n = 4 R=H (1) or R=3-NO 2 (2)
в качестве средства, обладающего антибактериальной активностью.as an antibacterial agent.
Комплексные соединения меди(II) на основе арилметиленбиспиран-2-онов были получены с использованием термической активации (см., например, Pozharov M.V. at al. Synthesis and characterization of copper (II) complexes with arylmethylenebis-4-hydroxy-6-methyl-2-N-pyran-2-ones: A case of interesting keto-enol tautomerism // Inorganica Chimica Acta. – 2021. – V. 517. – P. 120207-120216; и патент РФ № 2753853 по кл. МПК С07F 1/08, опуб. 24.08.2021).Copper(II) complexes based on arylmethylenebispyran-2-ones were obtained using thermal activation (see, for example, Pozharov MV at al. Synthesis and characterization of copper (II) complexes with arylmethylenebis-4-hydroxy-6-methyl- 2- N -pyran-2-ones: A case of interesting keto-enol tautomerism // Inorganica Chimica Acta. - 2021. - V. 517. - P. 120207-120216; and RF patent No. 2753853 according to IPC class С07F 1 /08, published 08/24/2021).
Соединение № 1 - комплекс меди(II) 3,3'-(фенилметилен)бис(4-гидрокси-6-метил-2Н-пиран-2-она) синтезирован одностадийным методом в результате двухкомпонентной реакции 3,3'-(фенилметилен)бис(4-гидрокси-6-метил-2Н-пиран-2-она) и моногидрата ацетата меди(II) в этаноле при термической активации.Compound No. 1 - copper(II) complex 3,3'-(phenylmethylene)bis(4-hydroxy-6-methyl-2H-pyran-2-one) was synthesized by a one-step method as a result of a two-component reaction 3,3'-(phenylmethylene) bis(4-hydroxy-6-methyl-2H-pyran-2-one) and copper(II) acetate monohydrate in ethanol with thermal activation.
Соединение № 2 - комплекс меди(II) 3,3'-((3-нитрофенил)метилен)бис(4-гидрокси-6-метил-2Н-пиран-2-она) синтезирован одностадийным методом в результате двухкомпонентной реакции 3,3'-((3-нитрофенил)метилен)бис(4-гидрокси-6-метил-2Н-пиран-2-она) и моногидрата ацетата меди(II) в этаноле при термической активации.Compound No. 2 - copper(II) complex 3,3'-((3-nitrophenyl)methylene)bis(4-hydroxy-6-methyl-2H-pyran-2-one) was synthesized by a one-step method as a result of a two-component reaction 3,3 '-((3-nitrophenyl)methylene)bis(4-hydroxy-6-methyl-2H-pyran-2-one) and copper(II) acetate monohydrate in ethanol with thermal activation.
Изобретение иллюстрируется чертежами, где представлены графики определения концентраций соединений, вызывающих 50% ингибирования роста бактериальной культуры Escherichia coli К 12, при этом:The invention is illustrated by drawings, which show graphs for determining the concentrations of compounds that cause 50% growth inhibition of the Escherichia coli K 12 bacterial culture , while:
- на фиг. 1 представлен график определения концентрации комплексного соединения № 1, вызывающего 50% ингибирования роста бактериальной культуры Escherichia coli;- in Fig. 1 is a graph for determining the concentration of complex compound No. 1, causing 50% growth inhibition of a bacterial culture of Escherichia coli ;
- на фиг. 2 представлен график определения концентрации комплексного соединения № 2, вызывающего 50% ингибирования роста бактериальной культуры Escherichia coli.- in Fig. 2 is a graph for determining the concentration of complex compound No. 2 causing 50% growth inhibition of Escherichia coli bacterial culture.
Антибактериальную активность комплексов меди(II) на основе арилметиленбиспиран-2-онов определяли на жидких питательных средах методом серийных разведений.The antibacterial activity of copper(II) complexes based on arylmethylenebispyran-2-ones was determined on liquid nutrient media by the method of serial dilutions.
Пример 1. Испытание антибактериальной активности комплексного соединения 1.Example 1. Testing the antibacterial activity of complex compound 1.
В 96-луночный планшет было внесено 0,16 мл среды LB + 0,04 мл раствора комплекса меди(II) 3,3'-(фенилметилен)бис(4-гидрокси-6-метил-2Н-пиран-2-она) в ДМСО в концентрации 10 мг/мл (раствор готовили путем растворения 4,3 мг комплекса меди(II) 3,3'-(фенилметилен)бис(4-гидрокси-6-метил-2Н-пиран-2-она в 0,43 мл ДМСО), затем сделан ряд двукратных разведений в диапазоне концентраций от 0,016 мг/мл до 2 мг/мл. После чего внесено по 0,100 мл бактериальной суспензии Escherichia coli K-12 (депонирован в IBPPM 204). В результате добавления бактериальной суспензии конечный диапазон исследуемых концентраций составил от 0,010 до 0,667 мг/мл. 0.16 ml LB medium + 0.04 ml copper(II) complex solution 3,3'-(phenylmethylene)bis(4-hydroxy-6-methyl-2H-pyran-2-one) was added to a 96-well plate in DMSO at a concentration of 10 mg/ml (the solution was prepared by dissolving 4.3 mg of the copper(II) complex 3,3'-(phenylmethylene)bis(4-hydroxy-6-methyl-2H-pyran-2-one in 0, 43 ml of DMSO), then a series of two-fold dilutions was made in the concentration range from 0.016 mg/ml to 2 mg/ml. the range of studied concentrations was from 0.010 to 0.667 mg/ml.
Планшет инкубировали в течение 6 часов при 37°С. Измеряли оптическую плотность D растворов на микропланшетном фотометре Multiskan Ascent (Thermo, Финляндия) при длине волны 620 нм. Контролем служили лунки с бактериальной культурой без внесения растворов исследуемых соединений. За проявление антибактериальной активности принималась более низкая оптическая плотность, чем в контрольных лунках.The tablet was incubated for 6 hours at 37°C. The optical density D of the solutions was measured on a Multiskan Ascent microplate photometer (Thermo, Finland) at a wavelength of 620 nm. Wells with a bacterial culture without adding solutions of the studied compounds served as the control. For the manifestation of antibacterial activity, a lower optical density was taken than in the control wells.
Пример 2. Испытание антибактериальной активности комплексного соединения 2.Example 2. Testing the antibacterial activity of complex compound 2.
В 96-луночный планшет было внесено 0,16 мл среды LB + 0,04 мл раствора комплекса меди(II) 3,3'-((3-нитрофенил)метилен)бис(4-гидрокси-6-метил-2Н-пиран-2-она) в ДМСО в концентрации 10 мг/мл (раствор готовили путем растворения 5,7 мг комплекса меди(II) 3,3'-((3-нитрофенил)метилен)бис(4-гидрокси-6-метил-2Н-пиран-2-она) в 0,57 мл ДМСО), затем сделан ряд двукратных разведений в диапазоне концентраций от 0,016 мг/мл до 2 мг/мл. После чего внесено по 0,100 мл бактериальной суспензии Escherichia coli K-12 (депонирован в IBPPM 204). В результате добавления бактериальной суспензии конечный диапазон исследуемых концентраций составил от 0,010 до 0,667 мг/мл. 0.16 ml LB medium + 0.04 ml copper(II) complex solution 3,3'-((3-nitrophenyl)methylene)bis(4-hydroxy-6-methyl-2H-pyran -2-one) in DMSO at a concentration of 10 mg/ml (the solution was prepared by dissolving 5.7 mg of copper(II) complex 3,3'-((3-nitrophenyl)methylene)bis(4-hydroxy-6-methyl- 2H-pyran-2-one) in 0.57 ml DMSO), then a series of two-fold dilutions was made in the concentration range from 0.016 mg/ml to 2 mg/ml. After that, 0.100 ml of a bacterial suspension of Escherichia coli K-12 (deposited in IBPPM 204) was added. As a result of the addition of the bacterial suspension, the final concentration range tested was from 0.010 to 0.667 mg/mL.
Планшет инкубировали в течение 6 часов при 37°С. Измеряли оптическую плотность D растворов на микропланшетном фотометре Multiskan Ascent (Thermo, Финляндия) при длине волны 620 нм. Контролем служили лунки с бактериальной культурой без внесения растворов исследуемых соединений. За проявление антибактериальной активности принималось более низкая оптическая плотность, чем в контрольных лунках.The tablet was incubated for 6 hours at 37°C. The optical density D of the solutions was measured on a Multiskan Ascent microplate photometer (Thermo, Finland) at a wavelength of 620 nm. Wells with a bacterial culture without adding solutions of the studied compounds served as the control. A lower optical density than in the control wells was taken as the manifestation of antibacterial activity.
Тестируемые вещества вносились в 5 повторах, эксперимент повторяли 3 раза.The test substances were added in 5 repetitions, the experiment was repeated 3 times.
В Таблице 1 представлены результаты определения антибактериальной активности соединений №1 и №2, для которых графически определены значения EC50 (концентрация соединения, вызывающая 50% ингибирование роста бактериальной культуры).Table 1 presents the results of the determination of the antibacterial activity of compounds No. 1 and No. 2, for which the EC 50 values (the concentration of the compound that causes 50% inhibition of the growth of the bacterial culture) are graphically determined.
На фиг. 1 кривая 1 соответствует лункам растворов соединения №1 без внесения в них бактериальной культуры, кривая 2 - лункам растворов соединения №1 с внесением в них бактериальной культуры, кривая 3 - лункам бактериальной культуры без внесения в них растворов соединения №1 (контроль). По линии «контроль 1/2" определено значение EC50 для комплекса меди(II) 3,3'-(фенилметилен)бис(4-гидрокси-6-метил-2Н-пиран-2-она).In FIG. Curve 1 in Fig. 1 corresponds to wells of solutions of compound No. 1 without adding a bacterial culture to them, curve 2 - to wells of solutions of compound No. 1 with adding a bacterial culture to them, curve 3 - to wells of a bacterial culture without adding solutions of compound No. 1 (control). The EC 50 value for the copper(II) complex 3,3'-(phenylmethylene)bis(4-hydroxy-6-methyl-2H-pyran-2-one) was determined along the "control 1/2" line.
На фиг. 2 кривая 1 соответствует лункам растворов соединения №2 без внесения в них бактериальной культуры, кривая 2 - лункам растворов соединения №2 с внесением в них бактериальной культуры, кривая 3 - лункам бактериальной культуры без внесения в них растворов соединения №2 (контроль). По линии «контроль 1/2" определено значение EC50 для комплекса меди(II) 3,3'-((3-нитрофенил)метилен)бис(4-гидрокси-6-метил-2Н-пиран-2-она).In FIG. Curve 1 in Fig. 2 corresponds to the wells of solutions of compound No. 2 without introducing a bacterial culture into them, curve 2 - to the wells of solutions of compound No. 2 with the introduction of a bacterial culture into them, curve 3 - to the wells of a bacterial culture without adding solutions of compound No. 2 (control). The EC 50 value for the copper(II) complex 3,3'-((3-nitrophenyl)methylene)bis(4-hydroxy-6-methyl-2H-pyran-2-one) was determined along the "control 1/2" line.
Таблица 1. Антибактериальная активность соединений №1 и №2.Table 1. Antibacterial activity of compounds No. 1 and No. 2.
По данным исследования можно сделать вывод, что комплексы меди(II) на основе арилметиленбиспиран-2-онов обладают антибактериальными свойствами по отношению к культуре клеток Escherichia coli в эффективном количестве.Based on the study data, it can be concluded that copper(II) complexes based on arylmethylenebispyran-2-ones have antibacterial properties in relation to the Escherichia coli cell culture in an effective amount.
Claims (4)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2786842C1 true RU2786842C1 (en) | 2022-12-26 |
Family
ID=
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2830172C1 (en) * | 2024-04-03 | 2024-11-14 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Саратовский национальный исследовательский государственный университет имени Н.Г. Чернышевского" | Hybrid compounds based on furan-2(3h)-one and chromene-4(4h)-thione, having antibacterial activity, and method for production thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012126354A1 (en) * | 2011-03-21 | 2012-09-27 | 北京华牧伟业科技有限公司 | Baicalin-copper complex, preparation method and application thereof |
| RU2706702C1 (en) * | 2019-06-20 | 2019-11-20 | Федеральное государственное бюджетное учреждение науки Институт органического синтеза им. И.Я. Постовского Уральского отделения Российской академии наук | Metal complexes based on polyfluorsalicylates and 1,10-phenanthroline with antibacterial activity and a method for production thereof |
| MD4652C1 (en) * | 2018-03-22 | 2020-04-30 | Государственный Университет Молд0 | Copper(II) sulfate complexes with 2-(2-hydroxybenzylidene)-N-(methoxyphenyl)hydrazinecarbothioamides exhibiting antimicrobial activity against gram-positive microorganisms |
| RU2753853C1 (en) * | 2020-03-16 | 2021-08-24 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Саратовский национальный исследовательский государственный университет имени Н.Г. Чернышевского" | Arilmethylene bispiran-2-one-based complex compounds of copper(ii) exhibiting cytotoxic activity to hela cell line |
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012126354A1 (en) * | 2011-03-21 | 2012-09-27 | 北京华牧伟业科技有限公司 | Baicalin-copper complex, preparation method and application thereof |
| MD4652C1 (en) * | 2018-03-22 | 2020-04-30 | Государственный Университет Молд0 | Copper(II) sulfate complexes with 2-(2-hydroxybenzylidene)-N-(methoxyphenyl)hydrazinecarbothioamides exhibiting antimicrobial activity against gram-positive microorganisms |
| RU2706702C1 (en) * | 2019-06-20 | 2019-11-20 | Федеральное государственное бюджетное учреждение науки Институт органического синтеза им. И.Я. Постовского Уральского отделения Российской академии наук | Metal complexes based on polyfluorsalicylates and 1,10-phenanthroline with antibacterial activity and a method for production thereof |
| RU2753853C1 (en) * | 2020-03-16 | 2021-08-24 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Саратовский национальный исследовательский государственный университет имени Н.Г. Чернышевского" | Arilmethylene bispiran-2-one-based complex compounds of copper(ii) exhibiting cytotoxic activity to hela cell line |
Non-Patent Citations (2)
| Title |
|---|
| AL-OBAIDI O.H., Synthesis and spectral study, theoretical evaluation of new binuclear Cr(III), Fe(III) and Zn(II) metal complexes derived from pyrane-2-one and its biological activity, TOFIQ Journal of Medical Science, 2015, v. 2, no. 2, p. 62-71. * |
| PATANGE V.N. at al., Synthesis, spectral, thermal and biological studies of transition metal complexes of 4-hydroxy-3-[3-(4-hydroxyphenyl)-acryloyl]-6-methyl-2H-pyran-2-one, J. Serb.Chem. Soc., 2011, v. 76, no. 9, p. 1237-1246. JADHAV S.M. at al., Synthesis, characterization, potentiometry, and antimicrobial studies of transition metal complexes of a tridentate ligand, J. Coord. Chem., 2010, v. 63, no. 23, p. 4153-4164. * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2830172C1 (en) * | 2024-04-03 | 2024-11-14 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Саратовский национальный исследовательский государственный университет имени Н.Г. Чернышевского" | Hybrid compounds based on furan-2(3h)-one and chromene-4(4h)-thione, having antibacterial activity, and method for production thereof |
| RU2835303C1 (en) * | 2024-07-23 | 2025-02-24 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Саратовский национальный исследовательский государственный университет имени Н.Г. Чернышевского" | 5-amino-1-(2,4-dinitrophenyl)-3-(3-nitrophenyl)-1h-pyrazole-4-carboxamide, having antimicrobial properties |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gümüş et al. | Synthesis, characterization and in vitro cytotoxic, mutagenic and antimicrobial activity of platinum (II) complexes with substituted benzimidazole ligands | |
| Creaven et al. | Biological activity and coordination modes of copper (II) complexes of Schiff base-derived coumarin ligands | |
| Saini et al. | Synthesis, characterization, and antibacterial activity of a novel heterocyclic Schiff’s base and its metal complexes of first transition series | |
| Savcı et al. | A new Schiff base containing 5-FU and its metal Complexes: Synthesis, Characterization, and biological activities | |
| Mjos et al. | Gallium (III) and iron (III) complexes of quinolone antimicrobials | |
| Maia et al. | Nickel (II) chloride Schiff base complex: Synthesis, characterization, toxicity, antibacterial and leishmanicidal activity | |
| Pahlavani et al. | A study on antitubercular and antimicrobial activity of isoniazid derivative | |
| Aslan et al. | Aromatic sulfonyl hydrazides and sulfonyl hydrazones: antimicrobial activity and physical properties | |
| Paulrasu et al. | Synthesis of 4-methyl-N′-(3-alkyl-2r, 6c-diarylpiperidin-4-ylidene)-1, 2, 3-thiadiazole-5-carbohydrazides with antioxidant, antitumor and antimicrobial activities | |
| Elshaarawy et al. | Antibacterial susceptibility of new copper (II) N-pyruvoyl anthranilate complexes against marine bacterial strains–In search of new antibiofouling candidate | |
| Sucheta et al. | Synthesis, SAR and in vitro therapeutic potentials of thiazolidine-2, 4-diones | |
| Yamamoto et al. | Copper (II) and silver (I) complexes with sulfamethizole: synthesis, spectroscopic characterization, ESI-QTOF mass spectrometric analysis, crystal structure and antibacterial activities | |
| Karadeniz et al. | Synthesis, structural studies and antimicrobial activity of N'-((2Z, 3E)-3-(hydroxyimino) butan-2-ylidene)-2-phenylacetohydrazide and its Co (II), Ni (II) complexes | |
| Tabrizi et al. | Synthesis, crystal structure and spectroscopy of bioactive Cd (II) polymeric complex of the non-steroidal anti-inflammatory drug diclofenac sodium: antiproliferative and biological activity | |
| Stojković et al. | Synthesis, characterization, antimicrobial and antitumor reactivity of new palladium (II) complexes with methionine and tryptophane coumarine derivatives | |
| Simić et al. | Newly synthesized palladium (II) complexes with aminothiazole derivatives: In vitro study of antimicrobial activity and antitumor activity on the human prostate cancer cell line | |
| Ertürk et al. | Antipyrine derived-Schiff base copper complex: Synthesis, characterization, and in vitro evaluation | |
| Al-Khazragie et al. | Synthesis, antimicrobial, antioxidant, toxicity and anticancer activity of a new azetidinone, thiazolidinone and selenazolidinone derivatives based on sulfonamide | |
| Kalaiarasi et al. | New cationic and neutral copper (II) complexes containing 7-hydroxy-4-oxo-4 [H]-chromene derived ONO pincer ligands: Synthesis, characterization and in vitro biological evaluations | |
| Karataş et al. | Water-soluble silver (I) complexes with N-donor benzimidazole ligands containing an imidazolium core: Stability and preliminary biological studies | |
| Ismail et al. | Novel imidazolium-thiohydantoin hybrids and their Mn (III) complexes for antimicrobial and anti-liver cancer applications | |
| Borthagaray et al. | Essential transition metal ion complexation as a strategy to improve the antimicrobial activity of organic drugs | |
| Kareem et al. | Synthesis, Characterization and Antimicrobial Studies of TransitionMetal Complexes with Azo Ligand derivative from 4-Aminoantipyrine | |
| RU2786842C1 (en) | Agent with antibacterial activity against escherichia coli cell culture | |
| Tian et al. | The manganese (II) and cobalt (II) complexes of enrofloxacin showed comparable antibacterial activity: Synthesis, crystal structure and antibacterial activity |