Cell cycle arrest and induction of apoptosis of newly synthesized pyranoquinoline derivatives under microwave irradiation
- 6 Downloads
A set of 2-amino-4-aryl-4H-pyrano[3,2-h]quinoline-3-carbonitrile derivatives were prepared via a one-pot, three-component condensation reaction between the substituted hydroxyquinoline derivatives, some aryl and/or hetaryl aldehydes, and malononitrile in an ethanol/piperidine solution in a microwave irradiation environment. The structure of the prepared compounds was instituted on the foundations of their spectral data: IR, 1H NMR, 13C NMR, and MS. Four human cancer cell lines, MCF-7, HCT-116, HepG-2, and A549 were utilized to evaluate the antiproliferative properties of the target compounds in comparison to the positive controls, Vinblastine and Colchicine using the MTT viability assay. The cell cycle arrest behavior, detected by propidium iodide as well as the apoptosis induction, which was monitored by the flow cytometer, using the Annexin V-FITC kits, was investigated. The results illustrated that the potent cytotoxic compounds induce cell cycle arrest at the G2/M phases and trigger apoptosis in the different tested cancer cells. Finally, the structure−activity relationship (SAR) study showcases the substitution of some specific groups at the 4-, 6-, and 9-positions in the prepared 2-amino-4H-pyrano[3,2-h]quinoline derivatives, which indicates that the lipophilicity manipulates the ability of these moieties against the diverse cell lines.
KeywordsMicrowave synthesis 4H-Pyrano[3,2-h]quinoline Antitumor Cell cycle SAR
The authors extend their appreciation to the Deanship of Science Research at King Khalid University for funding this work through General Research Project under Grant Number (G.R.P-168-39). In addition, the authors deeply thank the Regional Center for Mycology & Biotechnology (RCMP), Al-Azhar University, Cairo, Egypt, for carrying out the antitumor study and also, Mr. Ali Y. A. Alshahrani for drawing the 1H NMR and 13C NMR spectra.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Al-Ghamdi AM, Abd EL-Wahab AHF, Mohamed HM, El-Agrody AM (2012) Synthesis and antitumor activities of 4H-pyrano[3,2-h]quinoline-3-carbonitrile, 7H-pyrimido[4′,5′:6,5] pyrano[3,2-h]quinoline, and 14H-Pyrimido[4′,5′:6,5]pyrano[3,2-h][1,2,4]triazolo[1,5-c]quinoline derivative. Lett Drug Des Discov 9:459–470CrossRefGoogle Scholar
- Demirci F, Bas¸er KHC (2002) Bioassay techniques for drug development By Atta-ur-Rahman, M. Iqbal Choudhary (HEJRIC, University of Karachi, Pakistan), William J. Thomsen (Areana Pharmaceuticals, San Diego, CA). Harwood Academic Publishers, Amsterdam, the Netherlands. xii+223pp. J Nat Prod 65:1086–1087Google Scholar
- El-Agrody AM, Al-Ghamdi AM (2011) Synthesis of certain novel 4H-pyrano[3,2-h] quinoline derivatives ARKIVOC xi_134–146Google Scholar
- Hammouda MAA, EL-Hag FA-AA, El-Serwy WS, El-Manawaty MA (2015) Synthesis and characterization of new fused 4H-Pyranquinoline carbonitrile derivatives with anticipated antitumor biological activity. RJPBCS 6:200–208Google Scholar
- Hassanin HM, Ibrahim MA, Alnamer YA-S (2012) Synthesis and antimicrobial activity of some novel 4-hydroxyquinolin-2(1H)-ones and pyrano[3,2-c]quinolinones from 3-(1-ethy1-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-3-oxopropanoic acid. Turk J Chem 36:682–699Google Scholar
- Maalej E, Chabchoub F, Oset-Gasque MJ, Esquivias-Pérez M, González MP, Monjas L, Pérez C, de los Ríos C, Rodríguez-Franco MI, Iriepa I, Moraleda I, Chioua M, Romero A, Marco-Contelles J, Samadi A (2012) Synthesis, biological assessment, and molecular modeling of racemic 7-aryl-9,10,11,12-tetrahydro-7H-benzo[7,8]chromeno[2,3-b]quinolin-8-amines as potential drugs for the treatment of Alzheimer’s disease. Eur J Med Chem 54:750–763CrossRefGoogle Scholar
- Magesh CJ, Makesh SV, Perumal PT (2004) Highly diastereoselective inverse electron demand (IED) Diels–Alder reaction mediated by chiral salen–AlCl complex: the first, target-oriented synthesis of pyranoquinolines as potential antibacterial agents. Bioorg Med Chem Lett 14:2035–2040CrossRefGoogle Scholar
- Narsinh D, Anamik S (2001) Synthesis and anti-HIV studies of some substituted pyrimidinediones, ethoxy pyrano (3,2-C) quinolines and hydrazino pyrano (3,2-C) quinolines. Ind J Pharm Sci 63:211–215Google Scholar
- Qu Z, Cui J, Harata-Lee Y, Aung TN, Feng Q, Raison JM (2016) Identification of candidate anti-cancer molecular mechanisms of Compound Kushen Injection using functional genomics. Oncotarget 10:66003–66019Google Scholar
- Rahman AU, Choudhary MI, Thomsen WJ (2001) Bioassay technique for drug development. Harwood Academic Publishers, Reading, UK.Google Scholar
- Siliveri S, Radhika T, Harinadha BV, Raj S, Madhava RB (2017) Synthesis and biological evaluation of pyrano[3,2-h]quinoline carbonitriles. Int J Green Pharm 11:S423–S429Google Scholar