Biological Activity Evaluation of Novel 1,2,4-Triazine Derivatives Containing Thiazole/Benzothiazole Rings

• Published in: Anti-cancer agents in medicinal chemistry Vol. 17; no. 13; p. 1846
• Main Authors: Yurttas, Leyla, Ciftci, Gulsen Akalin, Temel, Halide Edip, Saglik, Begum Nurpelin, Demir, Bahar, Levent, Serkan
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2017
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Benzothiazoles - chemistry; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; Humans; Inhibitory Concentration 50; MCF-7 Cells; Mice; NIH 3T3 Cells; Structure-Activity Relationship; Thiazoles - chemistry; Triazines - chemistry; Triazines - pharmacology; lung cancer; Triazine; apoptosis; benzothiazole; antiproliferative activity; thiazole
• ISSN: 1875-5992
• DOI: 10.2174/1871520617666170327151031

Triazine ring is a prominent structural motif found in some azanucleosides whose efficiency improved many times in the research area of antitumor agents. In this study, we have designed and synthesized novel 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)thio]-N-(6- substituted benzo/(thiazol)-2-yl)acetamide (2a-d, 3a-f) derivatives using 1,2,4-triazine core along with two important heterocyles, thiazole and benzothiazole rings. The acquired ten final compounds were screened to investigate their antitumor activity against lung adenocarcinoma cell line, A549 and mouse fibroblast cell line, NIH/3T3. Five compounds with higher antiproliferative activity have been further studied to evaluate whether the cell death due to necrosis or apoptosis using flow cytometry. Compound 3b bearing 6-methylbenzothiazole moiety has been established as the most active antitumor compound with a selective profile and higher apoptotic cell level. All final componds were also screened against acetylcholine/butyrylcholinesterase enzymes to state their anticholinesterase activity.