Email this article 
Hide
Show all
OPEN ACCESS | 
PEER-REVIEWED |
RESEARCH ARTICLE
|
DOWNLOAD PDF
|
VIEW FULL-TEXT PDF
| TOTAL VIEWS
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 (4) , SubbaRao Venkata Madhunapantula (5) , Hulikal Shivashankara Santhosh Kumar (6) , Rajeshwara Achur (7) (1) Department of Biochemistry, Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India
(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
(3) Department of Pharmaceutical Chemistry, Kuvempu University Post Graduate Centre, Kadur, Karnataka-577548, India
(4) Department of Pharmaceutical Chemistry, Kuvempu University Post Graduate Centre, Kadur, Karnataka-577548, India
(5) 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
(6) Department of Biotechnology, Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India
(7) Department of Biochemistry, Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India
(*) Corresponding Author
Received: 10 Jul 2020 | Revised: 25 Aug 2020 | Accepted: 27 Aug 2020 | Published: 30 Sep 2020 | Issue Date: September 2020
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.
Keywords
Full Text:
PDF
DOI: 10.5155/eurjchem.11.3.223-234.2004
Links for Article
| | | | | | |
| | | | | | |
| | | |
Related Articles
Article Metrics
This Abstract was viewed 854 times |
PDF Article downloaded 355 times
Funding information
Kuvempu University, Jnana Sahyadri, Shimoga, Karnataka, 577451, India and Jagadguru Sri Shivarathreeshwara Academy of Higher Education and Research, Mysuru, Karnataka, 570015, India.
Citations
[1]. Sanjay D. Hadiyal, Jaydeep N. Lalpara, Bhavin B. Dhaduk, H. S. Joshi
Rational synthesis, anticancer activity, and molecular docking studies of novel benzofuran liked thiazole hybrids
Molecular Diversity , , 2022
DOI: 10.1007/s11030-022-10493-7
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
How to cite
The other citation formats (EndNote | Reference Manager | ProCite | BibTeX | RefWorks) for this article can be found online at: How to cite item
DOI Link: https://doi.org/10.5155/eurjchem.11.3.223-234.2004
| 
| 
| 
| 
| 
| 
| 
| 
| 
| 
| 
| 
| 
| 
| 
Save to Zotero
Save to Mendeley
European Journal of Chemistry 2020, 11(3), 223-234 | doi: https://doi.org/10.5155/eurjchem.11.3.223-234.2004 | Get rights and content
Refbacks
- There are currently no refbacks.
Copyright (c) 2020 Authors
This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry).
© Copyright 2010 - 2023 • Atlanta Publishing House LLC • All Right Reserved.
The opinions expressed in all articles published in European Journal of Chemistry are those of the specific author(s), and do not necessarily reflect the views of Atlanta Publishing House LLC, or European Journal of Chemistry, or any of its employees.
Copyright 2010-2023 Atlanta Publishing House LLC. All rights reserved. This site is owned and operated by Atlanta Publishing House LLC whose registered office is 2850 Smith Ridge Trce Peachtree Cor GA 30071-2636, USA. Registered in USA.