{"title":"噻吩衍生物的设计、合成、生物学评价和分子对接研究","authors":"Rashmi Shah, Prabhakar Kumar Verma, Manisha Shah, Satendra Kumar","doi":"10.1007/s13738-024-03088-6","DOIUrl":null,"url":null,"abstract":"<div><p>A series of 1-(2-amino-2,4,5,6,7,7a-hexahydrobenzo[<i>b</i>]-3-yl)-3-substitued-phenylpropane-1,3-dionederivatives were synthesized using the Gewald synthesis in first step which is followed by Baker−Venkataraman rearrangement to yield title compounds. The FTIR, MS and 1H NMR results of the produced derivatives were validated. The biological potential such as antimicrobial, antioxidant and antimycobacterial activity against a particularly virulent strain of MTB (MTB H37Ra) of the synthesized compounds were examined. Antimicrobial screening outcomes showed that compound <i>S</i><sub>17</sub> turned to be the most effective antibacterial agent against Gram positive bacteria such as <i>Staphylococcus aureus</i> (MIC = 16.87 µM) and <i>Bacillus subtilis</i> (MIC = 9.45 µM) and Gram negative bacteria such as <i>Escherichia coli</i> (MIC = 16.87 µM) and compound <i>S</i><sub>7</sub> against <i>Salmonella typhi</i> (MIC = 9.74 µM) and compound <i>S</i><sub>16</sub> displayed remarkable antifungal activity toward each <i>Candida albicans</i> and <i>Aspergillus niger</i> (MIC = 15.23 µM). The standard drugs, cefadroxil (antibacterial), have MIC value against <i>S. aureus, B. subtilis, E. coli</i> and <i>S. Typhi are</i> 16.40 µM, 32.80 µM, 16.40 µM and 16.40 µM, respectively, and fluconazole (antifungal) has MIC value 20.40 µM against both the <i>C. albicans</i> and <i>A.niger</i> strain. In comparison with ascorbic acid, a standard drug (IC<sub>50</sub> 44.91 µg/mL), compound <i>S</i><sub>10</sub> demonstrated good antioxidant activity, with an IC<sub>50</sub> value of 45.29 µg/mL, according to the results of the antioxidant screening. The results of the in vitro antituberculosis screening showed that compound <i>S</i><sub>23</sub> was found to be effective with an MIC value of 78.125 µg/mL. Molecular docking study of an enzymatic active site of “<i>DprE1-decaprenylphosphoryl-β-D-ribose-2′-epimerase</i>” shows a comparable binding mode to the native ligand with better docking score which contributes in understanding and development of models for ligand–protein interactions. Compound <i>S</i><sub>23</sub> showed better docking score of − 8.516 as compared to the Isoniazid with the docking score of − 6.315 which in future will create the fundamental structural framework for MTB inhibition.</p><h3>Graphic abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":676,"journal":{"name":"Journal of the Iranian Chemical Society","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design, synthesis, biological evaluation and molecular docking studies of thiophene derivatives\",\"authors\":\"Rashmi Shah, Prabhakar Kumar Verma, Manisha Shah, Satendra Kumar\",\"doi\":\"10.1007/s13738-024-03088-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>A series of 1-(2-amino-2,4,5,6,7,7a-hexahydrobenzo[<i>b</i>]-3-yl)-3-substitued-phenylpropane-1,3-dionederivatives were synthesized using the Gewald synthesis in first step which is followed by Baker−Venkataraman rearrangement to yield title compounds. The FTIR, MS and 1H NMR results of the produced derivatives were validated. The biological potential such as antimicrobial, antioxidant and antimycobacterial activity against a particularly virulent strain of MTB (MTB H37Ra) of the synthesized compounds were examined. Antimicrobial screening outcomes showed that compound <i>S</i><sub>17</sub> turned to be the most effective antibacterial agent against Gram positive bacteria such as <i>Staphylococcus aureus</i> (MIC = 16.87 µM) and <i>Bacillus subtilis</i> (MIC = 9.45 µM) and Gram negative bacteria such as <i>Escherichia coli</i> (MIC = 16.87 µM) and compound <i>S</i><sub>7</sub> against <i>Salmonella typhi</i> (MIC = 9.74 µM) and compound <i>S</i><sub>16</sub> displayed remarkable antifungal activity toward each <i>Candida albicans</i> and <i>Aspergillus niger</i> (MIC = 15.23 µM). The standard drugs, cefadroxil (antibacterial), have MIC value against <i>S. aureus, B. subtilis, E. coli</i> and <i>S. Typhi are</i> 16.40 µM, 32.80 µM, 16.40 µM and 16.40 µM, respectively, and fluconazole (antifungal) has MIC value 20.40 µM against both the <i>C. albicans</i> and <i>A.niger</i> strain. In comparison with ascorbic acid, a standard drug (IC<sub>50</sub> 44.91 µg/mL), compound <i>S</i><sub>10</sub> demonstrated good antioxidant activity, with an IC<sub>50</sub> value of 45.29 µg/mL, according to the results of the antioxidant screening. The results of the in vitro antituberculosis screening showed that compound <i>S</i><sub>23</sub> was found to be effective with an MIC value of 78.125 µg/mL. Molecular docking study of an enzymatic active site of “<i>DprE1-decaprenylphosphoryl-β-D-ribose-2′-epimerase</i>” shows a comparable binding mode to the native ligand with better docking score which contributes in understanding and development of models for ligand–protein interactions. Compound <i>S</i><sub>23</sub> showed better docking score of − 8.516 as compared to the Isoniazid with the docking score of − 6.315 which in future will create the fundamental structural framework for MTB inhibition.</p><h3>Graphic abstract</h3>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":676,\"journal\":{\"name\":\"Journal of the Iranian Chemical Society\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-09-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the Iranian Chemical Society\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s13738-024-03088-6\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Iranian Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s13738-024-03088-6","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Design, synthesis, biological evaluation and molecular docking studies of thiophene derivatives
A series of 1-(2-amino-2,4,5,6,7,7a-hexahydrobenzo[b]-3-yl)-3-substitued-phenylpropane-1,3-dionederivatives were synthesized using the Gewald synthesis in first step which is followed by Baker−Venkataraman rearrangement to yield title compounds. The FTIR, MS and 1H NMR results of the produced derivatives were validated. The biological potential such as antimicrobial, antioxidant and antimycobacterial activity against a particularly virulent strain of MTB (MTB H37Ra) of the synthesized compounds were examined. Antimicrobial screening outcomes showed that compound S17 turned to be the most effective antibacterial agent against Gram positive bacteria such as Staphylococcus aureus (MIC = 16.87 µM) and Bacillus subtilis (MIC = 9.45 µM) and Gram negative bacteria such as Escherichia coli (MIC = 16.87 µM) and compound S7 against Salmonella typhi (MIC = 9.74 µM) and compound S16 displayed remarkable antifungal activity toward each Candida albicans and Aspergillus niger (MIC = 15.23 µM). The standard drugs, cefadroxil (antibacterial), have MIC value against S. aureus, B. subtilis, E. coli and S. Typhi are 16.40 µM, 32.80 µM, 16.40 µM and 16.40 µM, respectively, and fluconazole (antifungal) has MIC value 20.40 µM against both the C. albicans and A.niger strain. In comparison with ascorbic acid, a standard drug (IC50 44.91 µg/mL), compound S10 demonstrated good antioxidant activity, with an IC50 value of 45.29 µg/mL, according to the results of the antioxidant screening. The results of the in vitro antituberculosis screening showed that compound S23 was found to be effective with an MIC value of 78.125 µg/mL. Molecular docking study of an enzymatic active site of “DprE1-decaprenylphosphoryl-β-D-ribose-2′-epimerase” shows a comparable binding mode to the native ligand with better docking score which contributes in understanding and development of models for ligand–protein interactions. Compound S23 showed better docking score of − 8.516 as compared to the Isoniazid with the docking score of − 6.315 which in future will create the fundamental structural framework for MTB inhibition.
期刊介绍:
JICS is an international journal covering general fields of chemistry. JICS welcomes high quality original papers in English dealing with experimental, theoretical and applied research related to all branches of chemistry. These include the fields of analytical, inorganic, organic and physical chemistry as well as the chemical biology area. Review articles discussing specific areas of chemistry of current chemical or biological importance are also published. JICS ensures visibility of your research results to a worldwide audience in science. You are kindly invited to submit your manuscript to the Editor-in-Chief or Regional Editor. All contributions in the form of original papers or short communications will be peer reviewed and published free of charge after acceptance.