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2-((1H-1,2,3-triazol-1-yl)methyl)-3-phenylquinazolin-4(3H)-ones: Design, Synthesis and Evaluation as Anti-cancer Agents

[ Vol. 14 , Issue. 3 ]

Author(s):

Kamala K. Vasu*, Hemantkumar D. Ingawale, Sneha R. Sagar, Jayesh A. Sharma, Dhaivat H. Pandya and Milee Agarwal   Pages 254 - 263 ( 10 )

Abstract:


Background: Prevalence of lung cancer and breast cancer is increasing worldwide. Current therapies have certain limitations for the treatment of lung cancer and breast cancer. We herewith report a series of novel 2-((1H-1,2,3-triazol-1-yl)methyl)-3-phenylquinazolin-4(3H)-ones as anticancer agents for the treatment of lung cancer and breast cancer.

Method: Synthesis of 2-((1H-1,2,3-triazol-1-yl)methyl)-3-phenylquinazolin-4(3H)-ones involves four steps. Step 1 is the formation of 2-(2-chloroacetamido)benzoic acid from 2-aminobenzoic acid by coupling with 2-chloroacetyl chloride, followed by step 2 which involves the formation of quinazolinone ring scaffold 2-(chloromethyl)-3-phenylquinazolin-4(3H)-ones on cyclisation with substituted anilines. Step 3 and 4 follow click chemistry approach of Huisgen's 1,3-dipolar cycloaddition which include conversion to 2-(azidomethyl)-3-phenylquinazolin-4(3H)-ones by sodium azide and further reaction with substituted alkynes to obtain 2-((1H-1,2,3-triazol-1-yl)methyl)-3-phenylquinazolin- 4(3H)-ones. All the molecules are characterized by spectral analysis and tested for anti-cancer activity against A-549 lung cancer and MDAMB-231 breast cancer cell lines using colorimetric MTT assay.

Results: Amongst the synthesized compounds, 3-(4-nitrophenyl)-2-((4-phenyl-1H-1,2,3-triazol-1- yl)methyl)quinazoline-4-(3H)-one 5i and 3-(2,4-Dimethoxyphenyl)-2-((4-phenyl-1H-1,2,3-triazol-1- yl)methyl)quinazoline-4(3H)-one 5o were found to be active based on cell viability assays using A- 549 lung and MDAMB-231 breast cancer cell lines.

Conclusion: Novel route for the synthesis of hitherto unknown 2-((1H-1,2,3-triazol-1-yl)methyl)-3- phenylquinazolin-4(3H)-ones was developed. All the molecules were tested for their anti-cancer activities and two molecules were shown to exhibit anti-cancer activity in micromolar range.

Keywords:

Click-chemistry, 1, 2, 3-Triazole, Quinazoline-4(3H)-one, 2-((1H-1, 2, 3-triazol-1-yl)methyl)-3-phenylquinazolin- 4(3H)-one, anti-cancer activity.

Affiliation:

Department of Medicinal Chemistry, B.V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S.G. Highway, Thaltej, Ahmedabad 380054, Gujarat, Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Ahmedabad; S.G. Highway, Thaltej, Ahmedabad 380054, Gujarat, Department of Medicinal Chemistry, B.V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S.G. Highway, Thaltej, Ahmedabad 380054, Gujarat, Department of Medicinal Chemistry, B.V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S.G. Highway, Thaltej, Ahmedabad 380054, Gujarat, Department of Medicinal Chemistry, B.V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S.G. Highway, Thaltej, Ahmedabad 380054, Gujarat, Department of Pharmacology and Toxicology, B.V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S.G. Highway, Thaltej, Ahmedabad 380054, Gujarat

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