Development of an Environment-Friendly and Electrochemical Method for the Synthesis of an Oxadiazole Drug-Scaffold That Targets Poly(ADP-Ribose)Polymerase in Human Breast Cancer Cells
The development of environment-friendly new Poly-adenosine diphosphate (ADP)-ribose Polymerase (PARP) inhibitors are highly essential because of their involvement in the survival of cancer cells. Therefore, a library of indazolyl-substituted-1,3,4-oxadiazoles known to inhibit PARP in cancer cells wa...
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MDPI AG
2023-08-01
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| author | Sindhu M. Parameshwaraiah Zhang Xi Akshay Ravish Arunkumar Mohan Vanishree Shankarnaik Dukanya Dukanya Shreeja Basappa Habbanakuppe D. Preetham Ganga Periyasamy Santhosh L. Gaonkar Peter E. Lobie Vijay Pandey Basappa Basappa |
| author_facet | Sindhu M. Parameshwaraiah Zhang Xi Akshay Ravish Arunkumar Mohan Vanishree Shankarnaik Dukanya Dukanya Shreeja Basappa Habbanakuppe D. Preetham Ganga Periyasamy Santhosh L. Gaonkar Peter E. Lobie Vijay Pandey Basappa Basappa |
| author_sort | Sindhu M. Parameshwaraiah |
| collection | DOAJ |
| description | The development of environment-friendly new Poly-adenosine diphosphate (ADP)-ribose Polymerase (PARP) inhibitors are highly essential because of their involvement in the survival of cancer cells. Therefore, a library of indazolyl-substituted-1,3,4-oxadiazoles known to inhibit PARP in cancer cells was synthesized by a green protocol. Furthermore, the cytotoxic effects of these compounds were evaluated in human MCF-7 breast cancer (BC) cells, which revealed that the compound 2-(3-bromo-4-nitrophenyl)-5-(1-methyl-1<i>H</i>-indazol-3-yl)-1,3,4-oxadiazole (<b>8</b>) inhibited viability with an IC<sub>50</sub> value of 1.57 µM. Since the oxadiazole structure was extensively used in medicinal chemistry applications, the reported environment-friendly protocol was superior to the conventional method. Further, computational mechanistic studies revealed that the oxadiazole ring formation occurred spontaneously when compared to the conventional method. Additionally, the in silico bioinformatic studies of oxadiazole binding towards PARP1 showed that compound <b>8</b> could bind to PARP1 with higher binding energy (BE) of −7.29 kcal/mol when compound to compound 5s (BE = −7.17 kcal/mol), a known PARP cleavage oxadiazole structure (2-(3,4-Dimethoxybenzyl)-5-(3-(2-fluoro-3-methylpyridin-4-yl)phenyl)-1,3,4-oxadiazole) indicative of the improvement in the optimization process. In conclusion, a newer indazolyl-oxadiazole compound is reported, which could serve as a lead in developing PARP inhibitors in BC cells. |
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| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-03-11T00:03:13Z |
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| spelling | doaj.art-4d8a33622ab94a81bc816b19cb72f9352023-11-19T00:35:24ZengMDPI AGCatalysts2073-43442023-08-01138118510.3390/catal13081185Development of an Environment-Friendly and Electrochemical Method for the Synthesis of an Oxadiazole Drug-Scaffold That Targets Poly(ADP-Ribose)Polymerase in Human Breast Cancer CellsSindhu M. Parameshwaraiah0Zhang Xi1Akshay Ravish2Arunkumar Mohan3Vanishree Shankarnaik4Dukanya Dukanya5Shreeja Basappa6Habbanakuppe D. Preetham7Ganga Periyasamy8Santhosh L. Gaonkar9Peter E. Lobie10Vijay Pandey11Basappa Basappa12Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, IndiaShenzhen Bay Laboratory, Shenzhen 518055, ChinaLaboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, IndiaLaboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, IndiaDepartment of Chemistry, Central College Campus, Bangalore University, Bangalore 560001, IndiaLaboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, IndiaDepartment of Chemistry, BITS-Pilani Hyderabad Campus, Jawahar Nagar, Medchal, Hyderabad 500078, IndiaLaboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, IndiaDepartment of Chemistry, Central College Campus, Bangalore University, Bangalore 560001, IndiaDepartment of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal 576104, IndiaShenzhen Bay Laboratory, Shenzhen 518055, ChinaTsinghua Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaLaboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, IndiaThe development of environment-friendly new Poly-adenosine diphosphate (ADP)-ribose Polymerase (PARP) inhibitors are highly essential because of their involvement in the survival of cancer cells. Therefore, a library of indazolyl-substituted-1,3,4-oxadiazoles known to inhibit PARP in cancer cells was synthesized by a green protocol. Furthermore, the cytotoxic effects of these compounds were evaluated in human MCF-7 breast cancer (BC) cells, which revealed that the compound 2-(3-bromo-4-nitrophenyl)-5-(1-methyl-1<i>H</i>-indazol-3-yl)-1,3,4-oxadiazole (<b>8</b>) inhibited viability with an IC<sub>50</sub> value of 1.57 µM. Since the oxadiazole structure was extensively used in medicinal chemistry applications, the reported environment-friendly protocol was superior to the conventional method. Further, computational mechanistic studies revealed that the oxadiazole ring formation occurred spontaneously when compared to the conventional method. Additionally, the in silico bioinformatic studies of oxadiazole binding towards PARP1 showed that compound <b>8</b> could bind to PARP1 with higher binding energy (BE) of −7.29 kcal/mol when compound to compound 5s (BE = −7.17 kcal/mol), a known PARP cleavage oxadiazole structure (2-(3,4-Dimethoxybenzyl)-5-(3-(2-fluoro-3-methylpyridin-4-yl)phenyl)-1,3,4-oxadiazole) indicative of the improvement in the optimization process. In conclusion, a newer indazolyl-oxadiazole compound is reported, which could serve as a lead in developing PARP inhibitors in BC cells.https://www.mdpi.com/2073-4344/13/8/11851,3,4-oxadiazolespoly(ADP-ribose) polymerasehuman breast cancerauto dockdensity function theory |
| spellingShingle | Sindhu M. Parameshwaraiah Zhang Xi Akshay Ravish Arunkumar Mohan Vanishree Shankarnaik Dukanya Dukanya Shreeja Basappa Habbanakuppe D. Preetham Ganga Periyasamy Santhosh L. Gaonkar Peter E. Lobie Vijay Pandey Basappa Basappa Development of an Environment-Friendly and Electrochemical Method for the Synthesis of an Oxadiazole Drug-Scaffold That Targets Poly(ADP-Ribose)Polymerase in Human Breast Cancer Cells Catalysts 1,3,4-oxadiazoles poly(ADP-ribose) polymerase human breast cancer auto dock density function theory |
| title | Development of an Environment-Friendly and Electrochemical Method for the Synthesis of an Oxadiazole Drug-Scaffold That Targets Poly(ADP-Ribose)Polymerase in Human Breast Cancer Cells |
| title_full | Development of an Environment-Friendly and Electrochemical Method for the Synthesis of an Oxadiazole Drug-Scaffold That Targets Poly(ADP-Ribose)Polymerase in Human Breast Cancer Cells |
| title_fullStr | Development of an Environment-Friendly and Electrochemical Method for the Synthesis of an Oxadiazole Drug-Scaffold That Targets Poly(ADP-Ribose)Polymerase in Human Breast Cancer Cells |
| title_full_unstemmed | Development of an Environment-Friendly and Electrochemical Method for the Synthesis of an Oxadiazole Drug-Scaffold That Targets Poly(ADP-Ribose)Polymerase in Human Breast Cancer Cells |
| title_short | Development of an Environment-Friendly and Electrochemical Method for the Synthesis of an Oxadiazole Drug-Scaffold That Targets Poly(ADP-Ribose)Polymerase in Human Breast Cancer Cells |
| title_sort | development of an environment friendly and electrochemical method for the synthesis of an oxadiazole drug scaffold that targets poly adp ribose polymerase in human breast cancer cells |
| topic | 1,3,4-oxadiazoles poly(ADP-ribose) polymerase human breast cancer auto dock density function theory |
| url | https://www.mdpi.com/2073-4344/13/8/1185 |
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