Molecular Docking, Antioxidant, Anticancer and Antileishmanial Effects of Newly Synthesized Quinoline Derivatives

Author(s): Zoonish Malghani, Arif-Ullah Khan*, Muhammad Faheem, Muhammad Z. Danish, Humaira Nadeem, Sameen F. Ansari, Madeeha Maqbool

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 13 , 2020

DOI : 10.2174/1871520620666200516145117

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Graphical Abstract:


Abstract:

Background: Due to the pressing need and adverse effects associated with the available anti-cancer agents, an attempt was made to develop the new anti-cancer agents with better activity and lesser adverse effects.

Objective: Synthetic approaches based on chemical modification of quinoline derivatives have been undertaken with the aim of improving anti-cancer agents’ safety profile.

Methods: In the present study, quinoline derivatives 6-hydroxy-2-(4-methoxyphenyl) quinoline-4-carboxylic acid (M1) and 2-(4-chlorophenyl)-6-hydroxyquinoline-4-carboxylic acid (M3) were synthesized by the reaction of aldehyde and pyruvic acid. The complete reaction was indicated by thin-layer chromatography. Newly synthesized M1and M3were tested for in silico and in vitro studies.

Results: M1 and M3 were docked against selected targets. Both the test compounds showed good affinity against all targets except the p300\CBP-associated factor target as there was no H-bond formed by M1. IC50 values of M1 and M3 against 1, 1-diphenyl-picrylhydrazyl free radical scavenging activity were 562 and 136.56ng/mL, respectively. In brine shrimp lethality assay, M1 and M3 showed IC50 value of 81.98 and 139.2ng/mL, respectively. IC50 values recorded for M1 and M3 in tumor inhibition activity were 129 and 219μg/mL, respectively. M1 and M3 exhibited concentration-dependent anti-cancer effects against human cell lines of hepatocellular carcinoma (HepG2) and colon cancer (HCT-116). Against HepG2 cells, M1 and M3 exhibited IC50 of 88.6 and 43.62μg/mL, respectively. M1 and M3 utilized against HCT-116 cell lines possessed IC50 values of 62.5 and 15.3μg/mL. M1 and M3 also showed an anti-leishmanial effect with IC50 values of 336.64 and 530.142μg/mL, respectively.

Conclusion: From the results of pharmacological studies, we conclude that the newly synthesized compound showed enhanced anti-oxidant, anti-cancer and anti-leishmanial profile with good yield.

Keywords: Molecular docking, anti-oxidant, anti-cancer, HepG2 cell line, HCT cell line, quinoline derivatives.

[1]
Varadhachary, G.R.; Tamm, E.P.; Abbruzzese, J.L.; Xiong, H.Q.; Crane, C.H.; Wang, H.; Lee, J.E.; Pisters, P.W.; Evans, D.B.; Wolff, R.A. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann. Surg. Oncol., 2006, 13(8), 1035-1046.
[http://dx.doi.org/10.1245/ASO.2006.08.011] [PMID: 16865597]
[2]
Rami, P.D.; Ball, J.J. Crowley. The IASLC Lung Cancer Staging Project. Proposals for revision of the T descriptors in the forthcoming (seventh) edition of the TNM Classification of Malignant tumour. J. Thorac. Oncol., 2007, 2, 593-602.
[http://dx.doi.org/10.1097/JTO.0b013e31807a2f81] [PMID: 17607114]
[3]
McBee, W., Jr; Gardiner, A.S.; Edwards, R.P.; Lesnock, J.; Bhargava, R. MicroRNA analysis in Human Papillomavirus (HPV)-associated cervical neoplasia and cancer. J. Carcinog. Mutagen., 2011, 1, 1-23.
[4]
Naga Deepthi, C.; Pavan, K.A.; Rameshbabu, I.U. Role of tumor suppressor protein p53 in apoptosis and cancer therapy. J. Cancer Sci. Ther., 2011, 17, 2-6.
[5]
Nair, A. Amplified hypoxia induced tumor-cell death. J. Carcinog. Mutagen., 2010, 1, 1-4.
[http://dx.doi.org/10.4172/2157-2518.1000109]
[6]
Nagy, M. HIF-1 is the commander of gateways to cancer. J. Cancer Sci. Ther., 2011, 3, 35-40.
[7]
Nutrition, Physical Activity, and the Prevention of Cancer: AGlobal Perspective; A.I.C.R: Washington DC. , 2007.
[8]
Byam, J.; Renz, J.; Millis, J.M. Liver transplantation for hepatocellular carcinoma. Hepatobiliary Surg. Nutr., 2013, 2(1), 22-30.
[PMID: 24570911]
[9]
Valenzuela, J.G.; Belkaid, Y.; Garfield, M.K.; Mendez, S.; Kamhawi, S.; Rowton, E.D.; Sacks, D.L.; Ribeiro, J.M. Toward a defined anti-Leishmania vaccine targeting vector antigens: Characterization of a protective salivary protein. J. Exp. Med., 2001, 194(3), 331-342.
[http://dx.doi.org/10.1084/jem.194.3.331] [PMID: 11489952]
[10]
Jones, L.P.; Buelto, D.; Tago, E.; Owusu-Boaitey, K.E. Abnormal mammary adipose tissue environment of BRCA1 mutant mice show a persistent deposition of highly vascularized multilocular adipocytes. J. Cancer Sci. Ther., 2011, 1(Suppl. 2), 4-12.
[http://dx.doi.org/10.4172/1948-5956.S2-004] [PMID: 24501658]
[11]
Chen, Y.L.; Huang, C.J.; Huang, Z.Y.; Tseng, C.H.; Chang, F.S.; Yang, S.H.; Lin, S.R.; Tzeng, C.C. Synthesis and antiproliferative evaluation of certain 4-anilino-8-methoxy-2-phenylquinoline and 4-anilino-8-hydroxy-2-phenylquinoline derivatives. Bioorg. Med. Chem., 2006, 14(9), 3098-3105.
[http://dx.doi.org/10.1016/j.bmc.2005.12.017] [PMID: 16412647]
[12]
Adsule, S.; Barve, V.; Chen, D.; Ahmed, F.; Dou, Q.P.; Padhye, S.; Sarkar, F.H. Novel Schiff base copper complexes of quinoline-2 carboxaldehyde as proteasome inhibitors in human prostate cancer cells. J. Med. Chem., 2006, 49(24), 7242-7246.
[http://dx.doi.org/10.1021/jm060712l] [PMID: 17125278]
[13]
Bhatt, H.G.; Agrawal, Y.K.; Patel, M.J. Amino and flouro-substituted quinoline-4-carboxylic acid derivatives. MWI synthesis cytotoxic activity, apoptotic DNA fragmentation and molecular docking studies. Med. Chem. Res., 2015, 24, 1162-11671.
[http://dx.doi.org/10.1007/s00044-014-1248-x]
[14]
Brand-Williams, W.; Cuvelier, M.E.; Berset, C. Use of free radical method to evaluate antioxidant activity. Lebensm. Wiss. Technol., 1995, 28, 25-30.
[http://dx.doi.org/10.1016/S0023-6438(95)80008-5]
[15]
Ahmad, B.; Azam, S.; Bashir, S.; Hussain, F.; Chaudhary, M.I. Insecticidal, brine shrimp cytotoxicity, antifungal and nitric oxide free radical scavenging activities of the aerial parts of Myrsine africana. Afr. J. Biotechnol., 2013, 10, 1448-1453.
[16]
Coker, P.S.; Radecke, J.; Guy, C.; Camper, N.D. Potato disc tumor induction assay: A multiple mode of drug action assay. Phytomedicine, 2003, 10(2-3), 133-138.
[http://dx.doi.org/10.1078/094471103321659834] [PMID: 12725566]
[17]
Morgan, D.M.L. Tetrazolium (MTT) assay for cellular viability and activity. Methods Mol. Biol., 1998, 79, 179-183.
[PMID: 9463833]
[18]
Mohebali, M.; Fotouhi, A.; Hooshmand, B.; Zarei, Z.; Akhoundi, B.; Rahnema, A.; Razaghian, A.R.; Kabir, M.J.; Nadim, A. Comparison of miltefosine and meglumine antimoniate for the treatment of Zoonotic Cutaneous Leishmaniasis (ZCL) by a randomized clinical trial in Iran. Acta Trop., 2007, 103(1), 33-40.
[http://dx.doi.org/10.1016/j.actatropica.2007.05.005] [PMID: 17586452]
[19]
Jorgensen, W.L. The many roles of computation in drug discovery. Science, 2004, 303(5665), 1813-1818.
[http://dx.doi.org/10.1126/science.1096361] [PMID: 15031495]
[20]
Hazuda, D.J.; Anthony, N.J.; Gomez, R.P.; Jolly, S.M.; Wai, J.S.; Zhuang, L.; Fisher, T.E.; Embrey, M.; Guare, J.P.J.R., Jr; Egbertson, M.S.; Vacca, J.P.; Huff, J.R.; Felock, P.J.; Witmer, M.V.; Stillmock, K.A.; Danovich, R.; Grobler, J.; Miller, M.D.; Espeseth, A.S.; Jin, L.; Chen, I.W.; Lin, J.H.; Kassahun, K.; Ellis, J.D.; Wong, B.K.; Xu, W.; Pearson, P.G.; Schleif, W.A.; Cortese, R.; Emini, E.; Summa, V.; Holloway, M.K.; Young, S.D. A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase. Proc. Natl. Acad. Sci. USA, 2004, 101(31), 11233-11238.
[http://dx.doi.org/10.1073/pnas.0402357101] [PMID: 15277684]
[21]
Schames, J.R.; Henchman, R.H.; Siegel, J.S.; Sotriffer, C.A.; Ni, H.; McCammon, J.A. Discovery of a novel binding trench in HIV integrase. J. Med. Chem., 2004, 47(8), 1879-1881.
[http://dx.doi.org/10.1021/jm0341913] [PMID: 15055986]
[22]
Stauffer, S.R.; Stanton, M.G.; Gregro, A.R.; Steinbeiser, M.A.; Shaffer, J.R.; Nantermet, P.G.; Barrow, J.C.; Rittle, K.E.; Collusi, D.; Espeseth, A.S.; Lai, M.T.; Pietrak, B.L.; Holloway, M.K.; McGaughey, G.B.; Munshi, S.K.; Hochman, J.H.; Simon, A.J.; Selnick, H.G.; Graham, S.L.; Vacca, J.P. Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind beta-secretase in a N-terminal 10s-loop down conformation. Bioorg. Med. Chem. Lett., 2007, 17(6), 1788-1792.
[http://dx.doi.org/10.1016/j.bmcl.2006.12.051] [PMID: 17257835]
[23]
de Lange, O.; Wolf, C.; Dietze, J.; Elsaesser, J.; Morbitzer, R.; Lahaye, T. Programmable DNA-binding proteins from Burkholderia provide a fresh perspective on the TALE-like repeat domain. Nucleic Acids Res., 2014, 42(11), 7436-7449.
[http://dx.doi.org/10.1093/nar/gku329] [PMID: 24792163]
[24]
Goodsell, D.S. Computational docking of biomolecular complexes with AutoDock. Cold Spring Harb. Protoc., 2009, 2009(5)prot5200
[http://dx.doi.org/10.1101/pdb.prot5200] [PMID: 20147154]
[25]
Mensor, L.L.; Menezes, F.S.; Leitão, G.G.; Reis, A.S.; dos Santos, T.C.; Coube, C.S.; Leitão, S.G. Screening of Brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. Phytother. Res., 2001, 15(2), 127-130.
[http://dx.doi.org/10.1002/ptr.687] [PMID: 11268111]
[26]
Meda, C.E.; Lamien, M.; Romito, J.; Millogo, O.G. Determination of the total phenolic, flavonoid and proline contents in Burkina Fasan honey, as well as their radical scavenging activity. Food Chem., 2005, 91, 71-577.
[http://dx.doi.org/10.1016/j.foodchem.2004.10.006]
[27]
Cui, K.; Luo, X.; Xu, K.; Ven Murthy, M.R. Role of oxidative stress in neurodegeneration: recent developments in assay methods for oxidative stress and nutraceutical antioxidants. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2004, 28(5), 771-799.
[http://dx.doi.org/10.1016/j.pnpbp.2004.05.023] [PMID: 15363603]
[28]
Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J.T.; Bokesch, H.; Kenney, S.; Boyd, M.R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 1990, 82(13), 1107-1112.
[http://dx.doi.org/10.1093/jnci/82.13.1107] [PMID: 2359136]
[29]
Katiyar, R.S.; Singhvi, N.R.; Kushwaha, R.V.; Ramji, L.; Suryanarayana, N.V.A. Mycorrhizal association in arjuna and jamun trees in forest of Bhandara region, Maharashtra, India. Int. J. Agric. Res., 2009, 4, 229-232.
[30]
Sassa, S.; Sugita, O.; Galbraith, R.A.; Kappas, A. Drug metabolism by the human hepatoma cell, Hep G2. Biochem. Biophys. Res. Commun., 1987, 143(1), 52-57.
[http://dx.doi.org/10.1016/0006-291X(87)90628-0] [PMID: 3030322]
[31]
El-Serag, H.B.; Tran, T.; Everhart, J.E. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology, 2004, 126(2), 460-468.
[http://dx.doi.org/10.1053/j.gastro.2003.10.065] [PMID: 14762783]


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Article Details

VOLUME: 20
ISSUE: 13
Year: 2020
Published on: 14 September, 2020
Page: [1516 - 1529]
Pages: 14
DOI: 10.2174/1871520620666200516145117
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