2D-Quantitative structure activity relationship (QSAR) modeling, docking studies, synthesis and in-vitro evaluation of 1,3,4-thiadiazole tethered coumarin derivatives as antiproliferative agents
Cancer is one of the leading causes of deaths globally. Despite many anticancer agents in the market, cancer stood as a major health concern to humanity due to the problems like drug resistance, toxicities and economic burden etc., and these issues strongly impose the scientists for the development...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-07-01
|
| Series: | Journal of Saudi Chemical Society |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319610321000843 |
| _version_ | 1818653143270948864 |
|---|---|
| author | Natarajan Ramalakshmi Pasumalai Manimegalai Richie R. Bhandare Subramani Arun Kumar Afzal B. Shaik |
| author_facet | Natarajan Ramalakshmi Pasumalai Manimegalai Richie R. Bhandare Subramani Arun Kumar Afzal B. Shaik |
| author_sort | Natarajan Ramalakshmi |
| collection | DOAJ |
| description | Cancer is one of the leading causes of deaths globally. Despite many anticancer agents in the market, cancer stood as a major health concern to humanity due to the problems like drug resistance, toxicities and economic burden etc., and these issues strongly impose the scientists for the development of novel anticancer agents. Hence, in the current investigation, we performed the 2D-QSAR (Quantitative Structure-Activity Relationship) analysis of a series of compounds reported with a potential antiproliferative activity using multiple regression analysis and designed compounds from the obtained QSAR model. The generated Multiple Linear Regression (MLR) equations were validated both internally and externally. The applicability domain has been done for the developed model. Based on the generated QSAR equations, a series of 2-amino-5-substituted-1,3,4-thiadiazole derivatives were designed and their antiproliferative activity was predicted using the QSAR equations. Further, molecular docking studies were carried out for the designed compounds using Autodock 4 against Epidermal Growth Factor Receptor (EGFR) kinase. The compounds with good binding affinity were synthesized and characterized by FT-IR, NMR and mass spectroscopy and evaluated for their antiproliferative activity against MCF-7 and PC3 cell lines considering the overexpression of EGFR kinase in breast and prostate cancers. The generated best model exhibited an r2 value of 0.93, q2LOO = 0.92, r2cv = 0.78. From the results, compound 3b and 3c exhibited good antiproliferative activity. The results of the study suggest that the synthesized active compound could serve as a lead for generating good biological agents against EGFR kinase. |
| first_indexed | 2024-12-17T02:33:13Z |
| format | Article |
| id | doaj.art-bc98793d4d87425db8233ade5ef6e39c |
| institution | Directory Open Access Journal |
| issn | 1319-6103 |
| language | English |
| last_indexed | 2024-12-17T02:33:13Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Saudi Chemical Society |
| spelling | doaj.art-bc98793d4d87425db8233ade5ef6e39c2022-12-21T22:06:55ZengElsevierJournal of Saudi Chemical Society1319-61032021-07-012571012792D-Quantitative structure activity relationship (QSAR) modeling, docking studies, synthesis and in-vitro evaluation of 1,3,4-thiadiazole tethered coumarin derivatives as antiproliferative agentsNatarajan Ramalakshmi0Pasumalai Manimegalai1Richie R. Bhandare2Subramani Arun Kumar3Afzal B. Shaik4Department of Pharmaceutical Chemistry, C. L. Baid Metha College of Pharmacy, Chennai, India; Corresponding authors at: Department of Pharmaceutical Chemistry, C. L. Baid Metha College of Pharmacy, Chennai, India (Ramalakshmi N); Department of Pharmaceutical Sciences, College of Pharmacy & Health Science, Ajman University, Ajman P.O. Box 346, United Arab Emirates (R.R. Bhandare); Department of Pharmaceutical Chemistry, Vignan Pharmacy College, Vadlamudi 522213, Andhra Pradesh, India (Afzal B. Shaik).Department of Pharmaceutical Chemistry, C. L. Baid Metha College of Pharmacy, Chennai, IndiaDepartment of Pharmaceutical Sciences, College of Pharmacy & Health Science, Ajman University, Ajman P.O. Box 346, United Arab Emirates; Center of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates; Corresponding authors at: Department of Pharmaceutical Chemistry, C. L. Baid Metha College of Pharmacy, Chennai, India (Ramalakshmi N); Department of Pharmaceutical Sciences, College of Pharmacy & Health Science, Ajman University, Ajman P.O. Box 346, United Arab Emirates (R.R. Bhandare); Department of Pharmaceutical Chemistry, Vignan Pharmacy College, Vadlamudi 522213, Andhra Pradesh, India (Afzal B. Shaik).SRM Modinagar College of Pharmacy, Srmist, Modinagar, Delhi NCR Campus, IndiaDepartment of Pharmaceutical Chemistry, Vignan Pharmacy College, Vadlamudi 522213, Andhra Pradesh, India; Corresponding authors at: Department of Pharmaceutical Chemistry, C. L. Baid Metha College of Pharmacy, Chennai, India (Ramalakshmi N); Department of Pharmaceutical Sciences, College of Pharmacy & Health Science, Ajman University, Ajman P.O. Box 346, United Arab Emirates (R.R. Bhandare); Department of Pharmaceutical Chemistry, Vignan Pharmacy College, Vadlamudi 522213, Andhra Pradesh, India (Afzal B. Shaik).Cancer is one of the leading causes of deaths globally. Despite many anticancer agents in the market, cancer stood as a major health concern to humanity due to the problems like drug resistance, toxicities and economic burden etc., and these issues strongly impose the scientists for the development of novel anticancer agents. Hence, in the current investigation, we performed the 2D-QSAR (Quantitative Structure-Activity Relationship) analysis of a series of compounds reported with a potential antiproliferative activity using multiple regression analysis and designed compounds from the obtained QSAR model. The generated Multiple Linear Regression (MLR) equations were validated both internally and externally. The applicability domain has been done for the developed model. Based on the generated QSAR equations, a series of 2-amino-5-substituted-1,3,4-thiadiazole derivatives were designed and their antiproliferative activity was predicted using the QSAR equations. Further, molecular docking studies were carried out for the designed compounds using Autodock 4 against Epidermal Growth Factor Receptor (EGFR) kinase. The compounds with good binding affinity were synthesized and characterized by FT-IR, NMR and mass spectroscopy and evaluated for their antiproliferative activity against MCF-7 and PC3 cell lines considering the overexpression of EGFR kinase in breast and prostate cancers. The generated best model exhibited an r2 value of 0.93, q2LOO = 0.92, r2cv = 0.78. From the results, compound 3b and 3c exhibited good antiproliferative activity. The results of the study suggest that the synthesized active compound could serve as a lead for generating good biological agents against EGFR kinase.http://www.sciencedirect.com/science/article/pii/S1319610321000843QSARAntiproliferativeThiadiazoleCoumarinDockingRegression |
| spellingShingle | Natarajan Ramalakshmi Pasumalai Manimegalai Richie R. Bhandare Subramani Arun Kumar Afzal B. Shaik 2D-Quantitative structure activity relationship (QSAR) modeling, docking studies, synthesis and in-vitro evaluation of 1,3,4-thiadiazole tethered coumarin derivatives as antiproliferative agents Journal of Saudi Chemical Society QSAR Antiproliferative Thiadiazole Coumarin Docking Regression |
| title | 2D-Quantitative structure activity relationship (QSAR) modeling, docking studies, synthesis and in-vitro evaluation of 1,3,4-thiadiazole tethered coumarin derivatives as antiproliferative agents |
| title_full | 2D-Quantitative structure activity relationship (QSAR) modeling, docking studies, synthesis and in-vitro evaluation of 1,3,4-thiadiazole tethered coumarin derivatives as antiproliferative agents |
| title_fullStr | 2D-Quantitative structure activity relationship (QSAR) modeling, docking studies, synthesis and in-vitro evaluation of 1,3,4-thiadiazole tethered coumarin derivatives as antiproliferative agents |
| title_full_unstemmed | 2D-Quantitative structure activity relationship (QSAR) modeling, docking studies, synthesis and in-vitro evaluation of 1,3,4-thiadiazole tethered coumarin derivatives as antiproliferative agents |
| title_short | 2D-Quantitative structure activity relationship (QSAR) modeling, docking studies, synthesis and in-vitro evaluation of 1,3,4-thiadiazole tethered coumarin derivatives as antiproliferative agents |
| title_sort | 2d quantitative structure activity relationship qsar modeling docking studies synthesis and in vitro evaluation of 1 3 4 thiadiazole tethered coumarin derivatives as antiproliferative agents |
| topic | QSAR Antiproliferative Thiadiazole Coumarin Docking Regression |
| url | http://www.sciencedirect.com/science/article/pii/S1319610321000843 |
| work_keys_str_mv | AT natarajanramalakshmi 2dquantitativestructureactivityrelationshipqsarmodelingdockingstudiessynthesisandinvitroevaluationof134thiadiazoletetheredcoumarinderivativesasantiproliferativeagents AT pasumalaimanimegalai 2dquantitativestructureactivityrelationshipqsarmodelingdockingstudiessynthesisandinvitroevaluationof134thiadiazoletetheredcoumarinderivativesasantiproliferativeagents AT richierbhandare 2dquantitativestructureactivityrelationshipqsarmodelingdockingstudiessynthesisandinvitroevaluationof134thiadiazoletetheredcoumarinderivativesasantiproliferativeagents AT subramaniarunkumar 2dquantitativestructureactivityrelationshipqsarmodelingdockingstudiessynthesisandinvitroevaluationof134thiadiazoletetheredcoumarinderivativesasantiproliferativeagents AT afzalbshaik 2dquantitativestructureactivityrelationshipqsarmodelingdockingstudiessynthesisandinvitroevaluationof134thiadiazoletetheredcoumarinderivativesasantiproliferativeagents |