Synthesis and anticancer effects evaluation of 1-alkyl-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl)benzo[d]thiazol-2-yl)urea as anticancer agents with low toxicity

Bioorganic & Medicinal Chemistry
Xiao-Xiao XieSan-Qi Zhang

Abstract

As a PI3K and mTOR dual inhibitor, N-(2-chloro-5-(2-acetylaminobenzo[d]thiazol-6-yl)pyridin-3-yl)-4-fluorophenylsulfonamide displays toxicity when orally administrated. In the present study, alkylurea moiety replaced the acetamide group in the compound and a series of 1-alkyl-3-(6-(2,3-disubstituted pyridin-5-yl)benzo[d]thiazol-2-yl)urea derivatives were synthesized. The antiproliferative activities of the synthesized compounds in vitro were evaluated against HCT116, MCF-7, U87 MG and A549 cell lines. The compounds with potent antiproliferative activity were tested for their acute oral toxicity and inhibitory activity against PI3Ks and mTORC1. The results indicate that the compound attached a 2-(dialkylamino)ethylurea moiety at the 2-positeion of benzothiazole can retain the antiproliferative activity and inhibitory activity against PI3K and mTOR. In addition, their acute oral toxicity reduced dramatically. Moreover, compound 2f can effectively inhibit tumor growth in a mice S180 homograft model. These findings suggest that 1-(2-dialkylaminoethyl)-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl)benzo[d]thiazol-2-yl)urea derivatives can serve as potent PI3K inhibitors and anticancer agents with low toxicity.

References

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Citations

Jul 18, 2019·Future Medicinal Chemistry·Adileh AyatiAlireza Foroumadi
Oct 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Thuraya Al-HarthyRaid Abdel-Jalil
Jan 21, 2021·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Seyedeh Roya Alizadeh, Seyedeh Mahdieh Hashemi
Apr 23, 2020·Bioorganic & Medicinal Chemistry Letters·Hao-Yue XiangChun-Hao Yang
Oct 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Liang XiaHeng Xu

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