Antiproliferative potential, quantitative structure-activity relationship, cheminformatic and molecular docking analysis of quinoline and benzofuran derivatives

Praveen Kumar; Chinnappa Apattira Uthaiah; Santhosha Sangapurada Mahantheshappa; Nayak Devappa Satyanarayan; SubbaRao Venkata Madhunapantula; Hulikal Shivashankara Santhosh Kumar; Rajeshwara Achur

doi:10.5155/eurjchem.11.3.223-234.2004

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Published: Sep 30, 2020

DOI: https://doi.org/10.5155/eurjchem.11.3.223-234.2004

Keywords:

QSAR, Autodock, Quinoline, Benzofuran, Molecular docking, Topoisomerase I and II

Section

Research Article

Issue

Vol. 11 No. 3 (2020): September 2020

Dates

Received 2020-07-10
Accepted 2020-08-27
Published 2020-09-30

Praveen Kumar

Department of Biochemistry, Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India

http://orcid.org/0000-0002-8034-6348

Chinnappa Apattira Uthaiah

Center of Excellence in Molecular Biology and Regenerative Medicine Laboratory, Department of Biochemistry, Jagadguru Sri Shivarathreeshwara Medical College, Jagadguru Sri Shivarathreeshwara Academy of Higher Education and Research, Mysuru, Karnataka, 570015, India

http://orcid.org/0000-0001-8606-8660

Santhosha Sangapurada Mahantheshappa

Department of Pharmaceutical Chemistry, Kuvempu University Post Graduate Centre, Kadur, Karnataka-577548, India

http://orcid.org/0000-0001-8734-2991

Nayak Devappa Satyanarayan

Department of Pharmaceutical Chemistry, Kuvempu University Post Graduate Centre, Kadur, Karnataka-577548, India

http://orcid.org/0000-0003-4511-3749

SubbaRao Venkata Madhunapantula

http://orcid.org/0000-0001-9167-9271

Hulikal Shivashankara Santhosh Kumar

Department of Biotechnology, Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India

http://orcid.org/0000-0003-0371-3535

Rajeshwara Achur

Department of Biochemistry, Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India

http://orcid.org/0000-0001-9867-8917

Abstract

Quinoline and benzofuran moieties are commonly used for the synthesis of therapeutically beneficial molecules and drugs since they possess a wide range of pharmacological activities including potent anticancer activity as compared to other heterocyclic compounds. Many of well-known antimalarial, antimicrobial, anti-helminthic, analgesic, anti-inflammatory, antiprotozoal, and antitumor compounds contain quinoline/benzofuran skeleton. The aim of this study was to analyze ten new quinoline and eighteen benzofuran derivatives for carcinoma cell line growth inhibition and to predict possible interactions with the target. The anticancer activity of these compounds against colon cancer (HCT-116) and triple-negative breast cancer (MDA-MB-468) cell lines was determined and performed molecular docking to predict the possible interactions. Among ten quinoline derivatives, Q1, Q4, Q6, Q9, and Q10 were found to be the most potent against HCT-116 and MDA-MB-468 with IC₅₀ values ranging from 6.2-99.6 and 2.7-23.6 μM, respectively. Using the IC₅₀ values, a model equation with quantitative structure activity relationship (QSAR) was generated with their descriptors such as HBA1, HBA2, kappa (1, 2 and 3), Balaban index, Wiener index, number of rotatable bonds, log S, log P and total polar surface area (TPSA). The effect of benzofuran derivatives was moderate in cytotoxicity tests and hence only quinolines were considered for further analysis. The molecular docking indicated the mammalian / mechanistic target of rapamycin (mTOR), Topoisomerase I and II as possible targets for these molecules. The predicted results obtained from QSAR and molecular docking analysis of quinoline derivatives showed high correlation in comparison to the results of the cytotoxic assay. Overall, this study indicated that quinolines are more potent as anticancer agents compared to benzofurans. Further, compound Q9 has emerged as a lead molecule which could be the base for further development of more potent anticancer agents.

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Kumar, P.; Uthaiah, C. A.; Mahantheshappa, S. S.; Satyanarayan, N. D.; Madhunapantula, S. V.; Kumar, H. S. S.; Achur, R. Antiproliferative Potential, Quantitative Structure-Activity Relationship, Cheminformatic and Molecular Docking Analysis of Quinoline and Benzofuran Derivatives. Eur. J. Chem. 2020, 11, 223-234.

Author Biographies

SubbaRao Venkata Madhunapantula, Center of Excellence in Molecular Biology and Regenerative Medicine Laboratory, Department of Biochemistry, Jagadguru Sri Shivarathreeshwara Medical College, Jagadguru Sri Shivarathreeshwara Academy of Higher Education and Research, Mysuru, Karnataka, 570015, India

Rajeshwara Achur, Department of Biochemistry, Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India

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Supporting Agencies

Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India and Jagadguru Sri Shivarathreeshwara Academy of Higher Education and Research, Mysuru, 570015, India.

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