Lemon Juice Mediated Synthesis of 3-Substituted Quinazolin-4(3H)-Ones and their Pharmacological Evaluation

Author(s):

Malavattu G. Prasad, C. Vijaya Lakshmi, Naresh K. Katari*, Sreekantha B. Jonnalagadda and Manojit Pal*   Pages 2001 - 2009 ( 9 )

Abstract:

<P>Background: Compounds containing the quinazoline-4(3H)-one framework constitute an important class of fused N-heterocycles that are found in more than 200 naturally occurring alkaloids. These compounds also show a diverse range of pharmacological activities including antitumor properties. This prompted us to explore a series of quinazolin-4-(3H)-one derivatives having no substituent at C-2 as potential cytotoxic agents. </P><P> Objective: The objective of this study was to synthesize and evaluate 3-substituted quinazolin-4(3H)-one derivatives for their potential cytotoxic properties. </P><P> Methods: A convenient method has been developed for the rapid synthesis of this class of compounds under a mild and non-hazardous reaction condition in good yields. The methodology involved a three-component reaction employing isatoic anhydride, amines and glyoxylic acid as reactants in the presence of lemon juice in PEG- 400 at room temperature (25-30ºC) under ultrasound irradiation. All the synthesized compounds were screened via an MTT assay for their potential cytotoxic properties in vitro using the cancerous cell lines e.g. A549, A2780, HepG2, K562, MCF-7 and HCT-116 and a non-cancerous HEK293 cell line. </P><P> Results: Several compounds such as 3a, 3b, 3d, 3e and 3f showed promising growth inhibition against these cancer cell lines but no significant effects on HEK293 cell line. The IC50 values of these compounds were comparable to doxorubicin whereas 3f significantly induced apoptosis in MCF-7 cells that also was comparable to doxorubicin. </P><P> Conclusion: An ultrasound-assisted MCR facilitated by lemon juice has been developed to synthesize 3- substituted quinazolin-4(3H)-one derivatives that could act as potential anticancer agents.</P>

Keywords:

Lemon juice, ultrasound, quinazolin-4(3H)-one derivatives, anticancer, alkaloids, MTT assay.

Affiliation:

Department of Chemistry, School of Science, GITAM (Deemed to be University), Hyderabad, Telangana, 502 329, Department of Chemistry, School of Science, GITAM (Deemed to be University), Hyderabad, Telangana, 502 329, Department of Chemistry, School of Science, GITAM (Deemed to be University), Hyderabad, Telangana, 502 329, School of Chemistry & Physics, College of Agriculture, Engineering & Science, Westville Campus, University of KwaZulu-Natal, P Bag X 54001, Durban 4000, Dr. Reddy&#39;s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad 500046

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