ANTIPROLIFERATIVE AND IN SILICO ADMET STUDY OF NEW 4-(PIPERIDIN-1-YLMETHYL)-2- (THIOPHEN-2-YL) QUINOLINE ANALOGUES
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i4.24147Keywords:
MTT assay, In silico, T-47D, HeLa, HepG2, MCF-7, MolinspirationAbstract
 Objective: Synthesis and antiproliferative study of novel 4-(piperidin-1-ylmethyl)-2-(thiophen-2-yl) quinoline 7(a-j) derivatives.
Methods: 4-(piperidin-1-ylmethyl)-2-(thiophen-2-yl) quinolines were synthesized by the addition of 4-(chloromethyl)-2-(thiophen-2-yl) quinoline (0.01 mol), piperidine (0.01 mol) in DMF (10 v) and K2CO3 (0.02 mol). The anticancer activity of the title compounds performed against T-47D, HeLa, HepG2, and MCF-7 human cancer cell lines growth was investigated by MTT assay.
Results: The compounds 7b and 7g exhibited 90% of the growth inhibitory effect on T-47D, HeLa, and MCF-7 and also 80% growth inhibition in HepG2 when compared with standard drug paclitaxel.
Conclusion: The synthesized compounds 4-(piperidin-1-ylmethyl)-2-(thiophen-2-yl) quinoline 7(a-j) exhibited a considerable degree of growth inhibition of human cancer cell lines. The synthesized molecules 7(a-j) are in acceptable range and are less toxic and can be considered as possible hits for drug discovery.
Downloads
References
Diaz-Cano SJ. Tumor heterogeneity: Mechanisms and bases for a reliable application of molecular marker design. Int J Mol Sci 2012;13:1951-2011.
Asad M, Daniel S, Mauro F. Redefining global health priorities: improving cancer care in developing settings. J Glob Health 2014;4(1):010304.
Reinberg S. Health Day News. Geneva: WHO; 2008.
Katritzky AR. Advances in Heterocyclic Chemistry. New York: Academic Press Publishes; 2002.
Dalvie DK, Kalgutkar AS, Khojasteh-Bakht SC, Obach RS, O’Donnell JP. Biotransformation reactions of five-membered aromatic heterocyclic rings. Chem Res Toxicol 2002;15:269-99.
Elsabee MZ, Ali EA, Mokhtar SM, Eweis M. Synthesis, characterization polymerization and antibacterial properties of novel thiophene substituted acrylamide. React Funct Polym 2011;71:1187-94.
Bonini C, Chiummiento L, Bonis MD, Funicello M, Lupattelli P, Suanno G, et al. Synthesis, biological activity and modelling studies of two novel anti HIV PR inhibitors with a thiophene containing hydroxyl ethyl amino core. Tetrahedron 2005;61:6580-9.
Ye D, Zhang Y, Wang F, Zheng M, Zhang X, Luo X, et al. Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity. Bioorg Med Chem 2010;18:1773-82.
Brandt W, Mologni L, Preu L, Lemcke T, Gambacorti-Passerini C, Kunick C, et al. Inhibitors of the RET tyrosine kinase based on a 2-(alkylsulfanyl)-4-(3-thienyl)nicotinonitrile scaffold. Eur J Med Chem 2010;45:2919-27.
Abdel WB, Abdel GH, Ghada EA, Badria FA. Synthesis, antimicrobial, antioxidant, antiinflammatory and analgesic activities of some new 3-(2′-thienyl)pyrazole based heterocycles. Med Chem Res 2012;21:1418-26.
Meotti FC, Silva DO, DosSantos AR, Zeni G, Rocha JB, Nogueira CW. Thiophene and furans derivatives: A new class of potential pharmacological agents. Environ Toxicol Pharmacol 2003;15:37-44.
Lu X, Wan B, Franzblau SG, You Q. Design, synthesis and anti-tubercular evaluation of new 2-acylated and 2-alkylated amino-5-(4-(benzyloxy)phenyl)thiophene-3-carboxylic acid derivatives. Part 1. Eur J Med Chem 2011;46:3551-63.
Amr AE, Sherif MH, Assy MG, Al OM, Ragab I. Antiarrhythmic, serotonin antagonist and antianxiety actvities of novel substituted thiophene derivatives synthesized from 2-amino-4,5,6,7-tetrahydro-N-phenylbenzo[b]thiophene -3-carboxamide. Eur J Med Chem 2010;45:5935-42.
Gonzalez JL, Stephens CE, Wenzler T, Brun R, Tanious FA, Wilson WD, et al. Synthesis and antiparasitic evaluation of bis-2,5-[4-guanidinophenyl]thiophenes. Eur J Med Chem 2007;42:552-7.
Romagnoli R, Baraldi PG, Carrion MD, Cara CL, Cruz-Lopez O, Preti D, et al. Design, synthesis, and biological evaluation of thiophene analogues of chalcones. Bioorg Med Chem 2008;16:5367-76.
Diana P, Carbone A, Barraja P, Montalbano A, Martorana A, Dattolo G, et al. Synthesis and antitumor properties of 2,5-bis(3’-indolyl)thiophenes: Analogues of marine alkaloid nortopsentin. Bioorg Med Chem Lett 2007;17:2342-6.
Gouda MA, Berghot MA, Baz EA, Hamama WS. Synthesis, antitumor and antioxidant evaluation of some new thiazole and thiophene derivatives incorporated coumarin moiety. Med Chem Res 2012;21:1062-70.
Scarpelli R, Di Marco A, Ferrigno F, Laufer R, Marcucci I, Muraglia E, et al. Studies of the metabolic stability in cells of 5-(trifluoroacetyl)thiophene-2-carboxamides and identification of more stable class II histone deacetylase (HDAC) inhibitors. Bioorg Med Chem Lett 2008;18:6078-82.
Firestone GL, Sundar SN. Anticancer activities of artemisinin and its bioactive derivatives. Expert Rev Mol Med 2009;11:e32.
Lu JJ, Meng LH, Cai YJ, Chen Q, Tong LJ, Lin LP, et al. Dihydroartemisinin induces apoptosis in HL-60 leukemia cells dependent of iron and p38 mitogen-activated protein kinase activation but independent of reactive oxygen species. Cancer Biol Ther 2008;7:1017-23.
Srivastava V, Negi AS, Kumar JK, Gupta MM, Khanuja SP. Plant-based anticancer molecules: A chemical and biological profile of some important leads. Bioorg Med Chem 2005;13:5892-908.
Micale N, Zappalà M, Grasso S. Synthesis and antitumor activity of 1,3-benzodioxole derivatives. Farmaco 2002;57:853-9.
Insuasty B, Orozco F, Quiroga J, Abonia R, Nogueras M, Cobo J, et al. Microwave induced synthesis of novel 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor agents. Eur J Med Chem 2008;43:1955-62.
Leite AC, daSilva KP, de Souza IA, deAraujo JM, Brondani DJ. Synthesis, antitumor and antimicrobial activities of new peptidyl derivatives containing the 1,3-benzodioxole system. Eur J Med Chem 2004;39:1059-65.
Al-Obaid AM, Abdel-Hamide SG, El-Kashef HA, Abdel-Aziz AA,El-Azab AS, Al-Khamees HA, et al. Substituted quinazolines, part 3. Synthesis, in vitro antitumor activity and molecular modeling study of certain 2-thieno-4(3H)-quinazolinone analogs. Eur J Med Chem 2009;44:2379-91.
Basnet A, Thapa P, Karki R, Choi H, Choi JH, Yun M, et al 2,6-dithienyl-4-furyl pyridines: Synthesis, topoisomerase I and II inhibition, cytotoxicity, structure-activity relationship, and docking study. Bioorg Med Chem Lett 2010;20:42-7.
Barresi V, Condorelli DF, Fortuna CG, Musumarra G, Scire S. In vitro antitumor activities of 2,6-di-[2-(Heteroaryl)vinyl]pyridines and pyridiniums. Bioorg Med Chem 2002;10:2899-904.
Anantacharya R, Manjulatha K, Satyanarayana ND, Santoshkumar S, Kaviraj MY. Antiproliferative, DNA cleavage and ADMET study of substituted 2-(1-benzofuran-2-yl)quinoline-4-carboxylic acid and its esters. Cogent Chem 2016;2:1158382.
Santoshkumar S, Manjulatha K, Satyanarayan ND, Anantacharya R, Harishkumar S, Harishkumar HN, et al. Antiproliferative, adme and potential in silico g6pdh inhibitory activity of novel 2-(1-benzofuran-2-yl)-4-(5-phenyl-4h-1, 2, 4-triazol-3- yl) quinoline derivatives. Int J Pharm Pharm Sci 2016;8:313-9.
Manjunatha KS, Satyanarayan ND, Harishkumar S. Antiproliferative and ADMET screening of novel 3-(1H-indol-3-yl)-1,3-diphenylpropan-1 one derivatives. Cogent Chem 2016;2:1172542.
Santhosha SM, Satyanarayan ND, Mahadevan KM, Yogesh DB, Menaka T. Synthesis, antiplasmodial and admet studies of 4-methylamino-2-phenylquinoline analogs. Int J Pharm Pharm Sci 2016;8:173-9.
Soulshekhar SP, Manjulatha K, Satyanarayan ND. Antiproliferative and DNA cleavage activity of various solvent extracts of Acacia farnesiana linn. Pod. Asian J Pharm Clin Res 2017;10:197-201.
Waring MJ, Arrowsmith J, Leach AR, Leeson PD, Mandrell S, Owen RM, et al. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat Rev Drug Discov 2015;14:475-86.
Feixiong C, Weihua L, Yadi Z, Jie S, Zengrui W, Guixia L. Admetsar: A comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 2012;52:3099-105.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immun Meth 1983;65:55-63.
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliver Rev 2001;46:3-26.
Hou T, Wang J. Structure-ADME relationship: Still a long way to go? Expert Opin Drug Metab Toxicol 2008;4:759-70.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
