European Journal of Chemistry 11 (3) (2020) 223-234 European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2020 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. http://dx.doi.org/10.5155/eurjchem.11.3.223-234.2004 European Journal of Chemistry View Journal Online View Article Online Antiproliferative potential, quantitative structure-activity relationship, cheminformatic and molecular docking analysis of quinoline and benzofuran derivatives Praveen Kumar 1 , Chinnappa Apattira Uthaiah 2 , Santhosha Sangapurada Mahantheshappa 3 , Nayak Devappa Satyanarayan 3 , SubbaRao Venkata Madhunapantula 2 , Hulikal Shivashankara Santhosh Kumar 4 and Rajeshwara Achur 1, * 1 Department of Biochemistry, Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India praveenbiochemku@gmail.com (P.K.), rajachur@gmail.com (R.A.) 2 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 auchinnappa16@gmail.com (C.A.U.), mvsstsubbarao@jssuni.edu.in (S.V.M.) 3 Department of Pharmaceutical Chemistry, Kuvempu University Post Graduate Centre, Kadur, Karnataka-577548, India santhosh.1507@rediffmail.com (S.S.M.), satya1782005@gmail.com (N.D.S.) 4 Department of Biotechnology, Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India sk.genesan@gmail.com (H.S.S.K.) * Corresponding author at: Department of Biochemistry, Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India. e-mail: anr@kuvempu.ac.in (R. Achur). 10.5155/eurjchem.11.3.223-234.2004 Received: 10 July 2020 Received in revised form: 25 August 2020 Accepted: 27 August 2020 Published online: 30 September 2020 Printed: 30 September 2020 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. QSAR Autodock Quinoline Benzofuran Molecular docking Topoisomerase I and II Cite this: Eur. J. Chem. 2020, 11(3), 223-234 Journal website: www.eurjchem.com 1. Introduction Cancer remains a major health issue causing high rates of morbidity and mortality worldwide. In low and middle-income countries, approximately 70% of deaths occur due to cancer. GLOBOCAN 2018 estimates the global cancer burden to be 18.1 million deaths, among which lung cancer is the leading cause of death (18.4% of all cancer deaths) in men and women. Among women, breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death [1]. Chemo- and radio-therapies are currently being used widely for treating cancer. These treatments are successful in a few cases, while in the majority of cases, it causes severe adverse effects that include drug-induced carcinoma, hepato- toxicity, tumorigenicity, and irritation of the skin due to lack of adequate target selectivity. Hence, novel anticancer drugs are being developed and selected by screening of combinatorial, chemical and virtual libraries, including small molecules, antibodies, peptides, and oligonucleotides [2]. ABSTRACT RESEARCH ARTICLE KEYWORDS