• Ahmed S. I. Mohamede Chemistry of Natural Compounds Department, National Research Centre, Dokki, Giza 12311, Egypt
  • Mohamed A. A. Elneairy Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt
  • Sanaa M Eldine Chemistry of Pesticides Department, National Research Centre, Dokki, Giza 12311, Egypt.


Quinolones, Pyrroloquinolines, Cycloaddition, Anti-tumor cytotoxicity


Objective: the present work aimed to synthesize novel quinoline and pyrroloquinoline derivatives and study their cytotoxic activity.

Methods: Diels–Alder reaction (4+2) was used for the synthesis of new quinolone and pyrrolo quinoline derivatives via the reactions of compound 1 with N-maleimide (4a-d) derivatives, ethyl acrylate (6) methylmethacrylate (8) and acetylene dicarboxylic acid (10). The synthesized compounds were characterized by NMR and Mass spectral data. Some of the synthesized compounds were screened for their antitumor activity against three different cell lines (MCF-7, HepG2 and HCT).

Results: The tested compounds exhibited antiproliferative activity against the three different cell lines, especially against MCF-7.

Conclusion: New quinoline and pyrroloquinoline derivatives were synthesized starting with 6-methyl-4-phenyl-2-thioxo-5-(4-methylphenylthio)-1,2-dihydropyridine-3-carbonitrile. Two new compounds 3 and 5a were tested for their in vitro antiproliferative activity against MCF-7, HepG2 and HCT cancer cell lines. The result showed that compound 3 exhibited more potent antiproliferative activity than compound 5a in case of MCF-7 and HCT cell lines.



Download data is not yet available.


Patrick G. An Introduction to medicinal chemistry. 4th edition. Oxford University Press: Oxford, UK; 2008.

Dürüst Y, Karaku H, Yavuz M, Gepdiremen A. Synthesis of novel triazoles bearing 1,2,4-oxadiazole and phenyl sulfonyl groups by 1,3-dipolar cycloaddition of some organic azides and their biological activities. Turk J Chem 2014;38:739-55.

Michael J. Quinoline, quinazoline and acridone alkaloids. Nat Prod Rep 2004;21:650–68.

Wu D. Towards new anticancer drugs. a decade of advances in the synthesis of camptothecins and related alkaloids. Tetrahedron 2003;59:8649–87.

Ghorab MM, Ragab FA, Hamed MM. Design, synthesis and anticancer evaluation of novel tetrahydroquinoline derivatives containing sulfonamide moiety. Eur J Med Chem 2009;44:4211-17.

Chilin A, Marzaro G, Marzano C, Dalla VL, Ferlin MG, Pastorini G, et al. Synthesis and antitumor activity of novel amsacrine analogs: the critical role of the acridine moiety in determining their biological activity. Bioorg Med Chem 2009;17:523-29.

Chen YL, Chen IL, Wang TC, Han CH, Tzeng CC. Novel mutations in the helix termination motif of keratin 3 and keratin 12 in 2 taiwanese families with meesmann corneal dystrophy. Eur J Med Chem 2005;40:928-32.

Chen YL, Zhao YL, Lu CM, Tzeng CC, Wang JP. Synthesis, cytotoxicity, and anti-inflammatory evaluation of 2-(furan-2-yl)-4-(phenoxy)quinoline derivatives. Part 4. Bioorg Med Chem 2006;14:4373-8.

Tseng CH, Chen YL, Lu PJ, Yang CN, Tzeng CC. Synthesis and antiproliferative evaluation of certain indeno[1,2-c]quinoline derivatives. Bioorg Med Chem 2008;16:3153-62.

Alqasoumi SI, Al-Taweel AM, Alafeefy AM, Hamed MM, Noaman E, Ghorab MM. Synthesis and biological evaluation of 2-amino-7,7-dimethyl4-substituted-5-oxo-1-(3,4,5-trimethoxy)-1,4,5,6,7,8-hexahydro-quinoline-3carbonitrile derivatives as potential cytotoxic agents. Bioorg Med Chem Lett 2009;19:6939-42.

Rashad AE, El-Sayed WA, Mohamed AM, Ali MM. Synthesis of new Quinoline derivatives as an inhibitor of human tumor cells growth. Arch Pharm 2010;343:440-8.

Ghorab MM, Ragab FA, Heiba HI, Arafa RK, El-Hossary EM. In vitro anticancer screening and radiosensitizing evaluation of some new quinolines and pyrimido[4,5-b]quinolines bearing a sulfonamide moiety. Eur J Med Chem 2010;45:3677-84.

Heiniger B, Gakhar G, Prasain K, Hua DH, Nguyen TA. Second-generation substituted quinolines as anticancer drugs for breast cancer. Antitumor Res 2010;30:3927-32.

Vezmar M, Georges E. Reversal of MRP-mediated doxorubicin resistance with quinoline-based drugs. Biochem Pharmacol 2000;59:1245-52.

Qiu H, Yashiro M, Zhang X, Miwa A, Hirakawa K. A FGFR2 inhibitor, Ki23057, enhances the chemosensitivity of drug-resistant gastric cancer cells. Cancer Lett 2011;307:47-52.

Caceres G, Robey RW, Sokol L, McGraw KL, Clark J, Lawrence NJ, et al. HG-829 Is a potent noncompetitive inhibitor of the ATP-Binding cassette multidrug resistance transporter ABCB1. Cancer Res 2012;72:4204-14.

Duan Z, Li X, Huang H, Yuan W, Zheng SL, Liu X, et al. Synthesis and evaluation of (2-(4-Methoxy phenyl)-4-quinolinyl)(2-piperidinyl)methanol (NSC23925) isomers to reverse multidrug resistance in cancer. J Med Chem 2012;55:3113-21.

Andrews S, Burgess SJ, Skaalrud D, Kelly JX, Peyton DH. Reversal agent and linker variants of reversed chloroquine. Activities against plasmodium falciparum. J Med Chem 2010;53:916-10.

Dalla VL, Gia O, Gasparotto V, Ferlin MG. Discovery of a new anilino-3H-pyrrolo[3,2-f]quinoline derivative as potential anti-cancer agent. Eur J Med Chem 2008;43:429-34.

Gasparotto E, Castagliuolo I, Chiarelotto G, Pezzi V, Montanaro D, Brun P, et al. Synthesis and biological activity of 7-Phenyl-6,9-dihydro-3H-pyrrolo[3,2-f]quinolin-9-ones: a new class of antimitotic agents devoid of aromatase activity. J Med Chem 2006;49:1910–5.

Sui Z, Altom J, Nguyen VN, Fernandez J, Bernstein JI, Hiliard JJ, et al. Synthesis and inhibitory activity of novel Tri-and tetracyclic quinolines against topoisomerases. Bioorg Med Chem 1998;6:735-42.

Legentil L, Benel L, Bertrand V, Lesur B, Delfourne E. Synthesis and antitumor characterization of pyrazolic analogues of the marine pyrroloquinoline alkaloids: wakayin and tsitsikammamines. J Med Chem 2006;49:2979–88.

Legentil L, Lesur B, Delfourne E. Aza-analogues of the marine pyrroloquinoline alkaloids wakayin and tsitsikammamines: synthesis and topoisomerase inhibition. Bioorg Med Chem Lett 2006;16:427–9.

Hilt G, Danz M. Regioselective cobalt-catalyzed diels-alder reaction towards 1,3-Disubstituted and 1,2,3-Trisubstituted benzene derivatives. Synthesis 2008;14:2257-63.

Ross A, Townsend S, Danishefsky S. Halocycloalkenones as diels-alder dienophiles. applications to generating useful structural patterns. J Org Chem 2013;78:204-10.

Sanyal A. Diels-Alder cycloaddition: cycloreversion A powerfull combo in materials designs. Macromol Chem Phys 2010;211:1417–25.

Elneairy MA, Eldine SM, Mohamed AS. Synthesis, Reactions and biological activity of pyridine 2-(1H)-Thione derivatives. Egypt J Appl Sci 2011;26:121-35.

Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 1990;82:1107-12.

Karthikeyan C, Narayana MN, Ramasamy S, Vanam U, Manivannan E, Karunagaran D, et al. Advances in chalcones with anticancer activities. Recent Pat Anti-Cancer Drug Discovery 2015;10:97-15.

Kamal A, Ramakrishna G, Raju P, Viswanath A, Ramaiah MJ, Balakishan G, et al. Synthesis and anticancer activity of chalcone linked imidazolones. Bioorg Med Chem Lett 2010;20:4865-9.

Yuanqing H, Ning C, Dengshun M. Biological effects of pyrroloquinoline quinone on liver damage in Bmi-1 knockout mice. Exp Ther Med 2015;10:451-8.

Akanksha M, Subhadeep R, Siddhartha M, Rajnish KY, Amit KK, Sudipta S. Antiproliferative effect of flower extracts of spilanthes paniculata on hepatic carcinoma cells. Int J Pharm Pharm Sci 2015;7:130-4.



How to Cite

Mohamede, A. S. I., M. A. A. Elneairy, and S. M. Eldine. “2,4-CYCLOADDITION REACTIONS: PREPARATION AND CYTOTOXICITY OF NOVEL QUINOLINE AND PYRROLO [3,4-F] QUINOLINE DERIVATIVES”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 12, Dec. 2015, pp. 64-68, https://journals.innovareacademics.in/index.php/ijpps/article/view/7788.



Original Article(s)