Potential anti-proliferative agents from 1,4-benzoxazinone-quinazolin-4(3H)-one templates

• Published in: Bioorganic & medicinal chemistry letters Vol. 27; no. 24; pp. 5481 - 5484
• Main Authors: Bollu, Rajitha, Banu, Saleha, Kasaboina, Suresh, Bantu, Rajashaker, Nagarapu, Lingaiah, Polepalli, Sowjanya, Jain, Nishant
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.12.2017; Elsevier
• Subjects: 1,4-Benzoxazinone; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Benzoxazines - chemistry; C[sbnd]C Coupling; Cell Line, Tumor; Cell lines; Cell Proliferation - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Drug Design; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Quinazolinone anti-proliferative; Quinazolinones - chemical synthesis; Quinazolinones - chemistry; Quinazolinones - pharmacology; Science & Technology; Structure-Activity Relationship; Quinazolinone anti-proliferative; CC Coupling; 1,4-Benzoxazinone; Cell lines; Apoptosis; DESIGN; ANALOGS; ANTICANCER AGENTS; ARYLATION; CHEMICALS; C-C Coupling; INHIBITORS; HECK REACTION; ANTAGONISTS; DERIVATIVES
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.10.044

A newly synthesized 1,4-benzoxazinone-acetylphenylallyl quinazolin-4(3H)-one hybrids 7a–n showed moderate to excellent anti-proliferative activity against A549, HeLa, MDA-MB-231human cancer cell lines. [Display omitted] Design strategy and anti-proliferative evaluation of new analogues 7a–n against A549, HeLa and MD-MB-231. •Novel 1,4-benzoxazinone-acetylphenylallyl quinazolins have been synthesized efficiently.•Evaluated for their anti-proliferative activity against four human cell lines.•Compounds 7a–n showed GI50 values ranging from 0.32 to 13.4 µM.•7f, 7j, 7l showed good anti-proliferative activity with GI50 values 0.58, 0.32, 0.37 µM. A novel synthetic protocol has been developed for the synthesis of 1,4-benzoxazinone-acetylphenylallyl quinazolin-4(3H)-one hybrids 7a–n by employing Pd-catalyzed CH arylation in presence of 5–10% phosphine ligand in good to excellent yields and evaluated for their anti-proliferative activity against three cancer cell lines such as A549 (lung), HeLa (cervical), MDA-MB-231 (breast). Compounds 7d, 7f, 7l and 7n exhibited promising anti-proliferative activity with GI50 values ranging from 0.37 to 2.73 µM respectively against A549, HeLa, and MDA-MB-231, while compound 7f showed significant activity against MDA-MB-231 with GI50 value 0.58 µM, 7j showed significant activity against A549 with GI50 value 0.32 µM and 7l showed significant activity against HeLa with GI50 value 0.37 µM. This is the first report on the synthesis and in vitro anti-proliferative evaluation of 1,4-benzoxazinone-acetylphenylallyl quinazolin-4(3H)-one hybrids.