Synthesis and screening of 2-(2-(4-substituted piperazine-1-yl)-5-phenylthiazol-4-yl)-3-aryl quinazolinone derivatives a
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Med Chem Res (2013) 22:2788–2794 DOI 10.1007/s00044-012-0260-2
ORIGINAL RESEARCH
Synthesis and screening of 2-(2-(4-substituted piperazine-1-yl)-5phenylthiazol-4-yl)-3-aryl quinazolinone derivatives as anticancer agents Ritesh N. Sharma • Rasik Ravani
Received: 24 November 2011 / Accepted: 22 September 2012 / Published online: 23 October 2012 Ó Springer Science+Business Media New York 2012
Abstract Synthesis of novel quinazolinone derivatives was performed from the reaction of N-benzoyl substituted piperazine-1-carbothioamide with 2-chloromethyl quinazolinone derivatives and screened for their in vitro cytotoxic activity by MTT assay. The cell lines used were NCI (human lung cancer cell), MCF 7 (Breast cancer cell), and HEK 293 (Normal epidermal kidney cell). Result of screening on cell line showed moderate to good anticancer activity for all the compounds. Compound 3d (IC50 = 1.1 ± 0.03 lM) was found to be the most active compared to standard methotrexate (IC50 = 2.20 ± 0.18 lM) and 5-florouracil (IC50 = 2.30 ± 0.49 lM). Structure activity relationship of synthesized analogs suggested that the presence of NH linker with aryl moiety at the third position of quinazolinone ring was important for potent anticancer activity. Electron donating group on phenyl ring at the third position of quinazolinone ring gave better anticancer activity then unsubstituted phenyl and electron withdrawing group. Activity by substituted piperazine at 2nd position of thiazole linked with quinazolinone scaffold gave better activity in the order of H [ CH3 [ CO–C6H5. Our findings may impart new direction to medicinal chemists and biochemists for further investigations of quinazolinone-thiazole containing anticancer agents. Keywords Anticancer Quinazolinone Thiazole Piperazine MTT assay
R. N. Sharma (&) R. Ravani Department of Pharmaceutical Chemistry, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Mahesana-Gozaria Highway, Ganpat Vidyanagar Dist., Mahesana 384012, Gujarat, India e-mail: [email protected]
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Introduction Cancer is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Number of cancer patients is increasing rapidly from day to day and good protection from cancer and with reduced adverse effects is the requirement of present scenario. Quinazolinones are among the most useful heterocyclic compound from both synthetic and medicinal chemistry aspects. Most of the researchers focused on synthesis of quinazolinone and their anticancer property (Ahmed et al., 2010; Shang et al., 2005). The structural design of quinazolinone have attracted a great deal of attention because of their ready accessibility, diverse chemical reactivity, and biological activities like anti-inflammatory (Ashok and Chatrasal, 2009), antimalarial (Shuren et al., 2010), anthelmintic (Rajiv and Anil, 2008), muscle relaxant (Buyuktimkin and Ekinici, 1992), antihyperlipidemic (Fawzia and Amry, 2005), antitubercular (Kunes et al., 2000), antimicrobial
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