Utility of 2-Methyl-quinazolin-4(3H)-one in the Synthesis of Heterocyclic Compounds with Anticancer Activity

Aisha Youssif Hassan Helali, Marwa Taha Mostafa Sarg, Makarem Mohamed Said Koraa, Mona Said Fathy El-Zoghbi

Department of Chemistry, Faculty of Science (Girls), Al-Azhar University, Cairo, Egypt.
Department of Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
Department of Organic Chemistry, Faculty of Pharmacy, Cairo University, Giza, Egypt.

DOI: 10.4236/ojmc.2014.41002                

Abstract

Quinolino[2,1-b]quinazolines 3 and 4, pyrrolo[2,1-b]quinazoline 5 and various substituted 2-(4-chlorostyryl)quinazoline derivatives including: 4-amino derivative 8, 4-hydrazino derivative 9, thiourea derivative 10, thiosemicarbazide derivative 19, 4-benzylidene hydrazinyl derivative 21, 4-amino thiazolidene derivatives 11, 12, 13, 22, imidazoquinazolines 15, 16, quinazolinium chloride 14, triazino[4,3-c]quinazolines 17, 18, tetrazino[1,6-c]quinazoline 20, 4-amino azetidinyl derivative 23, triazolo[4,3-c]quinazoline 24, 4-amino substituted quinazolines 25, 26, 27, 29 and quinazolino quinazoline 28 were synthesized through different chemical reactions. The obtained compounds were evaluated for their in vitro antitumor activity against HEPG2 and MCF-7 cell lines compared to the reference drug (doxorubicin). Compounds 18, 19, 20, 23 and 24 were found to be the most active against both cell lines exhibiting IC₅₀ values ranging from 10.82 - 29.46 μM/L and 7.09 - 31.85 μM/L against Hep-G2 and MCF-7 cell lines, respectively, in addition to docking study of these five compounds against thymidylate synthase and dihydrofolate reductase enzymes active sites.

Keywords

Quinazoline; Anticancer; DHFR; TS

Conflicts of Interest

The authors declare no conflicts of interest.

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