期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 37, 期 1, 页码 2765-2785出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2022.2130285
关键词
CA inhibitors; linkers flexibility; colony formation; wound healing; molecular dynamics
资金
- Faculty of Pharmacy, Tanta University
- Deanship of scientific research at Umm AlQura University [22UQU4290565DSR86]
This study reported the design and synthesis of two series of twenty-two benzenesulfonamides incorporating the s-triazine moiety, which successfully suppressed hCA IX and exhibited significant anticancer activity in various cancer cell lines.
Herein we reported the design and synthesis of two series comprising twenty-two benzenesulfonamides that integrate the s-triazine moiety. Target compounds successfully suppressed the hCA IX, with IC50 ranging from 28.6 to 871 nM. Compounds 5d, 11b, 5b, and 7b were the most active analogues, which inhibited hCA IX isoform in the low nanomolar range (K (I) = 28.6, 31.9, 33.4, and 36.6 nM, respectively). Furthermore, they were assessed for their cytotoxic activity against a panel of 60 cancer cell lines following US-NCI protocol. According to five-dose assay, 13c showed significant anticancer activity than 5c with GI(50)-MID values of 25.08 and 189.01 mu M, respectively. Additionally, 13c's effects on wound healing, cell cycle disruption, and apoptosis induction in NCI-H460 cancer cells were examined. Further, docking studies combined with molecular dynamic simulation showed a stable complex with high binding affinity of 5d to hCA IX, exploiting a favourable H-bond and lipophilic interactions.
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