European Journal of Chemistry

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

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

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.

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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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References

[1]. Bray, F.; Ferlay, J.; Soerjomataram. I.; Siegel, R. L.; Torre, L. A.; Jemal, A. CA-Cancer J. Clinic. 2018, 68(6), 394-424.
https://doi.org/10.3322/caac.21492

[2]. Mukherjee, A. K.; Basu, S.; Sarkar, N.; Ghosh, A. C. Curr. Med. Chem. 2001, 8(12), 1467-1486.
https://doi.org/10.2174/0929867013372094

[3]. Janku, F.; McConkey, D. J.; Hong, D. S.; Kurzrock, R. Nat. Rev. Clin. Oncol. 2011, 8(9), 528-539.
https://doi.org/10.1038/nrclinonc.2011.71

[4]. Green, J. A.; Kirwan, J. J.; Tierney. J.; Vale, C. L.; Symonds, P. R.; Fresco, L. L.; Williams, C.; Collingwood, M. Cochrane Database Syst. Rev. 2005, (3), CD002225.

[5]. DeVita, V. T.; Chu, E. Cancer Res. 2008, 68(21), 8643-8653.
https://doi.org/10.1158/0008-5472.CAN-07-6611

[6]. Chu, X. M.; Wang, C.; Liu, W.; Liang, L. L.; Gong, K. K.; Zhao, C. Y.; Sun, K. L. Eur. J. Med. Chem. 2019, 161, 101-117.
https://doi.org/10.1016/j.ejmech.2018.10.035

[7]. Ushio-Fukai, M.; Alexander, R. W. Mol. Cell Biochem. 2004, 264(1-2), 85-97.
https://doi.org/10.1023/B:MCBI.0000044378.09409.b5

[8]. Santoshkumar, S.; Satyanarayan, N. D.; Anantacharya, R.; Sameer, P. Int. J. Pharm. Pharm. Sci. 2017, 9, 260-267.

[9]. Slobbe, P.; Ruijter, E.; Orru, R. V. Med. Chem. Comm. 2012, 3(10), 1189-1218.
https://doi.org/10.1039/c2md20089a

[10]. Bates, J. G.; Clarke, A.; Kenney, T. F.; Kusam, S.; Tannheimer, S.; Gilead Sciences Inc, assignee. Combination of a bcl-2 inhibitor and a bromodomain inhibitor for treating cancer. United States patent application US 15/790, 434. May 17, 2018.

[11]. Santhosha, S. M.; Synthesis and pharmacological evaluation of novel quinoline derivatives, Ph.D thesis, Kuvempu University, 2017.

[12]. Anantacharya, R.; Manjulatha. K.; Satyanarayan, N. D.; Santoshkumar, S.; Kaviraj, M. Y. Cogent. Chem. 2016, 2(1), 1158382.
https://doi.org/10.1080/23312009.2016.1158382

[13]. Huey, R.; Morris, G. M.; Using AutoDock 4 with AutoDocktools, a tutorial. The Scripps Research Institute, 54-6, 2008, USA.

[14]. Vichai, V.; Kirtikara, K. Nat. Protoc. 2006, 1(3), 1112-1116.
https://doi.org/10.1038/nprot.2006.179

[15]. Orellana, E. A.; Kasinski, A. L. Bio-protocol 2016, 6(21), e1984.
https://doi.org/10.21769/BioProtoc.1984

[16]. De, Oliveira, D. B.; Gaudio, A. C. Quant. Struct. Act. Relat. 2000,19(6), 599-601.
https://doi.org/10.1002/1521-3838(200012)19:6<599::AID-QSAR599>3.0.CO;2-B

[17]. Dong, J.; Cao, D. S.; Miao, H. Y.; Liu, S.; Deng, B. C.; Yun, Y. H.; Wang, N. N.; Lu, A. P.; Zeng, W. B.; Chen, A. F. J. Cheminformatics. 2015, 7(1), 60.
https://doi.org/10.1186/s13321-015-0109-z

[18]. Smith, R. Y.; Smellie, A.; Mehta, N.; Inventors; PerkinElmer Informatics Inc, assignee. Systems and methods for translating three dimensional graphic molecular models to computer aided design format. United States patent US 9,751,294; Sep 5, 2017.

[19]. Gfeller, D.; Grosdidier, A.; Wirth, M.; Daina, A.; Michielin, O.; Zoete, V. Nucleic Acids Res. 2014, 42(W1), W32-W38.
https://doi.org/10.1093/nar/gku293

[20]. Cheminformatics, M. Calculation of molecular properties and bioactivity score, Retrieved on January 26, 2019, from http://www.molinspiration.com

[21]. Van, Aalten, D. M.; Bywater, R.; Findlay, J. B.; Hendlich, M.; Hooft, R. W.; Vriend, G. J. Comput. Aided Mol. Des. 1996, 10(3), 255-262.
https://doi.org/10.1007/BF00355047

[22]. Bernstein, F. C.; Koetzle, T. F.; Williams, G. J.; Meyer, Jr, E. F.; Brice, M. D.; Rodgers, J. R.; Kennard, O.; Shimanouchi, T.; Tasumi, M. Eur. J. Biochem. 1977, 80(2), 319-324.
https://doi.org/10.1111/j.1432-1033.1977.tb11885.x

[23]. Goddard, T. D.; Huang, C. C.; Ferrin, T. E. J. Struct. Biol. 2007, 157(1), 281-287.
https://doi.org/10.1016/j.jsb.2006.06.010

[24]. O'Boyle, N. M.; Banck, M.; James, C. A.; Morley, C.; Vandermeersch, T.; Hutchison, G. R. J. Cheminformatics. 2011, 3(1), 33.
https://doi.org/10.1186/1758-2946-3-33

[25]. Dallakyan, S.; Olson, A. J. Methods Mol. Biol. 2015, 1263, 243-250.
https://doi.org/10.1007/978-1-4939-2269-7_19

[26]. Biovia, D. S. Discovery studio visualizer, San Diego, CA, USA, 2017.

[27]. Willett, P. Comput. Mol. Sci. 2011, 1(1), 46-56.
https://doi.org/10.1002/wcms.1

[28]. Hammer, O.; Harper, D. A. T.; Ryan, P. D. Palaeontol Electron. 2001, 4(1), 1-9.

[29]. Alam, S.; Khan, F. Drug Des. Dev. Ther. 2014, 8, 183-195.

[30]. Rahmani, N.; Abbasi-Radmoghaddam, Z.; Riahi, S.; Mohammadi-Khanaposhtanai M. Struct. Chem. 2020, 25, 1-7.

[31]. Oluiua, J.; Nikolica, K.; Vucicevica, J.; Gagicb, Z.; Filipica, S.; Agbabaa, D.; QSAR modeling and structure based virtual screening of new PI3K/mTOR inhibitors as potential anticancer agents. InCMBEBIH 2017, Proceedings of the International Conference on Medical and Biological Engineering, Vol. 62, p. 379, Springer, 2017.
https://doi.org/10.1007/978-981-10-4166-2_58

[32]. Arthur, D. E.; Uzairu, A. J. Chin. Chem. Soc. Taip. 2018, 65(10), 1160-1178.
https://doi.org/10.1002/jccs.201700314

[33]. Chauhan, M.; Joshi, G.; Kler, H.; Kashyap, A.; Amrutkar, S. M.; Sharma, P.; Bhilare, K. D.; Banerjee, U. C.; Singh, S.; Kumar, R. RSC Adv. 2016, 6, 77717-77734.
https://doi.org/10.1039/C6RA15118C

[34]. Frisch, M. J.; Trucks G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; A. J. Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc. , Gaussian 09, Revision A. 02, Wallingford CT, 2009.

[35]. Osterberg, F.; Morris, G. M.; Sanner, M. F.; Olson, A. J.; Goodsell, D. S. Proteins 2002, 46(1), 34-40.
https://doi.org/10.1002/prot.10028

[36]. Li, H. T.; Zhu, X. Curr. Top. Med. Chem. 2020, 94(7), 1396-1417.

[37]. Jin, L. P.; Xie, Q.; Huang, E. F.; Wang, L.; Zhang, B. Q.; Hu, J. S.; Wan, D. C.; Jin, Z.; Hu, C. Bioorg. Chem. 2020, 95, 103566.
https://doi.org/10.1016/j.bioorg.2020.103566

[38]. Singh, A.; Sing, R. Open Bioinforma. J. 2013, 7, 63-67.
https://doi.org/10.2174/1875036201307010063

[39]. Li, S.; He, H.; Parthiban, L. J.; Yin, H.; Serajuddin, A. T. J. Pharm. Sci. 2005, 94(7), 1396-1417.
https://doi.org/10.1002/jps.20378

[40]. Bocker, A. J. Chem. Inf. Model. 2008, 48(11), 2097-2107.
https://doi.org/10.1021/ci8000887

[41]. Bhattacharya, S.; Zhang, Q.; Carmichael, P. L.; Boekelheide, K.; Andersen, M. E. PloS one. 2011, 6(6), e20887.
https://doi.org/10.1371/journal.pone.0020887

[42]. Kumar, S.; Kumar, Guru, S.; Venkateswarlu, V.; Malik, F.; A, Vishwakarma, R. D.; Sawant, S.; Bhushan, S. Anti-cancer Agent Me. 2015, 15(10), 1297-304.
https://doi.org/10.2174/1871520615666150402093558

[43]. Venkateswarlu, V.; Pathania, A. S.; Kumar, K. A.; Mahajan, P.; Nargotra, A.; Vishwakarma, R. A.; Malik, F. A.; Sawant, S. D. Bioorg. Med. Chem. 2015, 23(15), 4237-4247.
https://doi.org/10.1016/j.bmc.2015.06.046

[44]. Kundu, B.; Das, S. K.; Paul, Chowdhuri, S.; Pal, S.; Sarkar, D.; Ghosh, A.; Mukherjee, A.; Bhattacharya, D.; Das, B. B.; Talukdar, A. J. Med. Chem. 2019, 62(7), 3428-3446.
https://doi.org/10.1021/acs.jmedchem.8b01938

[45]. Pal, S.; Kumar, V.; Kundu, B.; Bhattacharya, D.; Preethy, N.; Reddy, M. P.; Talukdar, A.; Comput. Struct. Biotec. 2019, 17, 291-310.
https://doi.org/10.1016/j.csbj.2019.02.006

[46]. Staker, B. L.; Feese, M. D.; Cushman, M.; Pommier, Y.; Zembower, D.; Stewart, L.; Burgin, A. B. J. Med. Chem. 2005, 48(7), 2336-2345.
https://doi.org/10.1021/jm049146p

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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