Identification of N-arylsulfonylpyrimidones as anticancer agents

• Published in: Archives of pharmacal research Vol. 41; no. 3; pp. 251 - 258
• Main Authors: Subramanian, Santhosh, Boggu, Pulla Reddy, Yun, Jieun, Jung, Sang-Hun
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.03.2018; 대한약학회
• Subjects: antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - toxicity; Arylsulfonates - chemical synthesis; Arylsulfonates - toxicity; breasts; Cell Line, Tumor; colon; Drug Screening Assays, Antitumor - methods; human cell lines; Humans; lungs; Medicine; moieties; neoplasm cells; Pharmacology/Toxicology; Pharmacy; Pyrimidinones - chemical synthesis; Pyrimidinones - toxicity; Research Article; stomach; Structure-Activity Relationship; 약학; arylsulfonylpyrimidones; Antimitotic agent; arylsulfonyltetrahydropyrimidones; Anticancer activity; N-arylsulfonyltetrahydropyrimidones; N-arylsulfonylpyrimidones
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-018-1003-9

For confirming the role of five membered ring of imidazolidinone moiety of N -arylsulfonylimidazolidinones ( 7 ) previously reported with highly potent anticancer agent, a series of N -arylsulfonylpyrimidones ( 10a–g ) and N -arylsulfonyltetrahydropyrimidones ( 11a–e ) were prepared and their anti-proliferating activity was measured against human cancer cell lines (renal ACHN, colon HCT-15, breast MDA-MB-231, lung NCI-H23, stomach NUGC-3, and prostate PC-3) using XTT assay. Among them, 1-(1-acetylindolin-5-ylsulfonyl)-4-phenyltetrahydropyrimidin-2(1 H )-one ( 11d , mean GI 50  = 3.50 µM) and ethyl 5-(2-oxo-4-phenyltetrahydropyrimidin-1(2 H )-ylsulfonyl)-indoline-1-carboxylate ( 11e , mean GI 50  = 0.26 µM) showed best growth inhibitory activity against human cancer cell lines. Considering the activity results, N -arylsulfonyltetrahydropyrimidones ( 11 ) exhibited more potent activity compared to N -arylsulfonylpyrimidones ( 10 ) and comparable activity to N -arylsulfonylimidazolidinones ( 7 ). Especially, tetrahydropyrimidin-2(1 H )-one analogs containing acylindolin-5-ylsulfonyl moiety at position 1 demonstrated their strong growth inhibitory activity against human cancer cell lines.