{"title":"吡唑-1,2,4-三唑复合物的合成及生物活性评价:计算机辅助对接研究","authors":"Naga Mohan Mallisetty, Hanumantharao Ganipisetti, Debendra Majhi, Raju Sirisilla, Venkata Nagendra Kumar Putta","doi":"10.2174/1570163820666221125121625","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In the present study, a new series of 1,2,4-triazole linked to pyrazole derivatives (8a-j) of 4-(((7-amino-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazol-6-yl)methyl)amino)-1,5-dimethyl- 2-phenyl-1H-pyrazol-3(2H)-one were synthesized and assessed for their antibacterial and anticancer activity.</p><p><strong>Objective: </strong>Encouraged by these results, these analogues 4-(((7-amino-7H-[1,2,4]triazolo[4,3- b][1,2,4]triazol-6-yl)methyl)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-ones 8 have been synthesized and their inhibitory potential activity against different bacterial microorganisms and cancer cell lines was discussed.</p><p><strong>Methods: </strong>All the synthesized final scaffolds were characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR, IR, mass and elemental analysis. All the synthesized 1,2,4-triazole linked to pyrazole compounds were evaluated for their antimicrobial sensitivity by using the agar dilution technique. The anticancer activity of these compounds has been assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and docking results are described by Autodock 4.2.</p><p><strong>Results: </strong>In vitro analysis suggests that compounds 8h, 8f, and 8b demonstrated excellent antibacterial activity against S. aureus, P. aeruginosa, S. epidermidis with MICs of 8, 8, 11 μg/mL respectively, while the remaining compounds showed moderate to good inhibitory potential. Some of them exhibited potent cytotoxicity against MCF-7 and P388 cancer cell lines and compounds 8c, 8f, and 8d reveal the highest potency against MCF-7 with IC<sub>50</sub> values 2.8 ± 0.4, 3.1 ± 0.4, 3.5 ± 0.2 μM, respectively. Especially 8c, 8i and 8f showed better interaction patterns with amino acids Ala197 (N-N), Lys168 (N-N), Asn163 (O-N) at 3.13, 3.09, 3.00 A° as reported in DNA (Topo II) complex (1ZXM).</p><p><strong>Conclusion: </strong>New findings have established the fact that fused 1,2,4-triazoles linked to pyrazole contributed great significance in the field of medicinal chemistry due to their various biological properties.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"20 2","pages":"e251122211263"},"PeriodicalIF":0.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Synthesis and Biological Activity Evaluation of Pyrazole-1,2,4-triazole Hybrids: A Computer-aided Docking Studies.\",\"authors\":\"Naga Mohan Mallisetty, Hanumantharao Ganipisetti, Debendra Majhi, Raju Sirisilla, Venkata Nagendra Kumar Putta\",\"doi\":\"10.2174/1570163820666221125121625\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>In the present study, a new series of 1,2,4-triazole linked to pyrazole derivatives (8a-j) of 4-(((7-amino-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazol-6-yl)methyl)amino)-1,5-dimethyl- 2-phenyl-1H-pyrazol-3(2H)-one were synthesized and assessed for their antibacterial and anticancer activity.</p><p><strong>Objective: </strong>Encouraged by these results, these analogues 4-(((7-amino-7H-[1,2,4]triazolo[4,3- b][1,2,4]triazol-6-yl)methyl)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-ones 8 have been synthesized and their inhibitory potential activity against different bacterial microorganisms and cancer cell lines was discussed.</p><p><strong>Methods: </strong>All the synthesized final scaffolds were characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR, IR, mass and elemental analysis. All the synthesized 1,2,4-triazole linked to pyrazole compounds were evaluated for their antimicrobial sensitivity by using the agar dilution technique. The anticancer activity of these compounds has been assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and docking results are described by Autodock 4.2.</p><p><strong>Results: </strong>In vitro analysis suggests that compounds 8h, 8f, and 8b demonstrated excellent antibacterial activity against S. aureus, P. aeruginosa, S. epidermidis with MICs of 8, 8, 11 μg/mL respectively, while the remaining compounds showed moderate to good inhibitory potential. Some of them exhibited potent cytotoxicity against MCF-7 and P388 cancer cell lines and compounds 8c, 8f, and 8d reveal the highest potency against MCF-7 with IC<sub>50</sub> values 2.8 ± 0.4, 3.1 ± 0.4, 3.5 ± 0.2 μM, respectively. Especially 8c, 8i and 8f showed better interaction patterns with amino acids Ala197 (N-N), Lys168 (N-N), Asn163 (O-N) at 3.13, 3.09, 3.00 A° as reported in DNA (Topo II) complex (1ZXM).</p><p><strong>Conclusion: </strong>New findings have established the fact that fused 1,2,4-triazoles linked to pyrazole contributed great significance in the field of medicinal chemistry due to their various biological properties.</p>\",\"PeriodicalId\":10858,\"journal\":{\"name\":\"Current drug discovery technologies\",\"volume\":\"20 2\",\"pages\":\"e251122211263\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current drug discovery technologies\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/1570163820666221125121625\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current drug discovery technologies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1570163820666221125121625","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
Synthesis and Biological Activity Evaluation of Pyrazole-1,2,4-triazole Hybrids: A Computer-aided Docking Studies.
Background: In the present study, a new series of 1,2,4-triazole linked to pyrazole derivatives (8a-j) of 4-(((7-amino-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazol-6-yl)methyl)amino)-1,5-dimethyl- 2-phenyl-1H-pyrazol-3(2H)-one were synthesized and assessed for their antibacterial and anticancer activity.
Objective: Encouraged by these results, these analogues 4-(((7-amino-7H-[1,2,4]triazolo[4,3- b][1,2,4]triazol-6-yl)methyl)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-ones 8 have been synthesized and their inhibitory potential activity against different bacterial microorganisms and cancer cell lines was discussed.
Methods: All the synthesized final scaffolds were characterized by 1H NMR, 13C NMR, IR, mass and elemental analysis. All the synthesized 1,2,4-triazole linked to pyrazole compounds were evaluated for their antimicrobial sensitivity by using the agar dilution technique. The anticancer activity of these compounds has been assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and docking results are described by Autodock 4.2.
Results: In vitro analysis suggests that compounds 8h, 8f, and 8b demonstrated excellent antibacterial activity against S. aureus, P. aeruginosa, S. epidermidis with MICs of 8, 8, 11 μg/mL respectively, while the remaining compounds showed moderate to good inhibitory potential. Some of them exhibited potent cytotoxicity against MCF-7 and P388 cancer cell lines and compounds 8c, 8f, and 8d reveal the highest potency against MCF-7 with IC50 values 2.8 ± 0.4, 3.1 ± 0.4, 3.5 ± 0.2 μM, respectively. Especially 8c, 8i and 8f showed better interaction patterns with amino acids Ala197 (N-N), Lys168 (N-N), Asn163 (O-N) at 3.13, 3.09, 3.00 A° as reported in DNA (Topo II) complex (1ZXM).
Conclusion: New findings have established the fact that fused 1,2,4-triazoles linked to pyrazole contributed great significance in the field of medicinal chemistry due to their various biological properties.
期刊介绍：
Due to the plethora of new approaches being used in modern drug discovery by the pharmaceutical industry, Current Drug Discovery Technologies has been established to provide comprehensive overviews of all the major modern techniques and technologies used in drug design and discovery. The journal is the forum for publishing both original research papers and reviews describing novel approaches and cutting edge technologies used in all stages of drug discovery. The journal addresses the multidimensional challenges of drug discovery science including integration issues of the drug discovery process.
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