title: Design, synthesis and biological evaluation of novel 1,2,4-triazolo [3,4-b][1,3,4] thiadiazines bearing furan and thiophene nucleus.
abstract: Twenty-six novel 1,2,4-triazolo [3,4-b][1,3,4] thiadiazines containing furan and thiophene nucleus were designed, synthesized and evaluated for their antiproliferative activities. The results indicated that most of the compounds showed moderate to potent antiproliferative activities against four cancer cell lines, PC-3, HepG2, A549, and MCF-7. Particularly, compound 32 showed eleven-, three-, and two-fold improvement compared to positive control fluorouracil in inhibiting HepG2, PC-3, and A549 cell proliferation with IC₅₀ values of 5.09, 3.70 and 12.74 μM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 32 displayed a signiﬁcant effect on G2/M cell-cycle arrest in a dose-dependent manner in PC-3 cells. These encouraging results should provide important information for the development of new anticancer agents.
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Chen
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: En-Shan
authors.initials: ES
authors.lastname: Pan
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: youww@smu.edu.cn.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: You
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: plzhao@smu.edu.cn.
authors.forename: Pei-Liang
authors.initials: PL
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013876:Thiophenes / Q000737:chemistry*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000607136:(6-(thiophen-2-yl)-3-(3,4,5-trimethoxyphenyl)-6,7-dihydro-5H-(1,2,4)triazolo(3,4-b)(1,3,4)thiadiazin-7-yl)(p-tolyl)methanone; D000970:Antineoplastic Agents; D005663:Furans; D013829:Thiadiazines; D013876:Thiophenes; D014230:Triazoles; C039281:furan
keywords: 1,2,4-Triazolo [3,4-b][1,3,4] thiadiazine; Antiproliferative activity; Furan; Thiophene