Epoxy compounds usually have stronger nucleophilic ability, because the alkyl group on the oxygen atom makes the bond angle smaller, which makes the lone pair of electrons react more dissimilarly with the electron-deficient system. Compound: Picolinoyl chloride hydrochloride, is researched, Molecular C6H5Cl2NO, CAS is 39901-94-5, about New SIRT2 inhibitors: Histidine-based bleomycin spin-off.Electric Literature of C6H5Cl2NO.
Bleomycin is considered to exert its antitumor activity via DNA cleavage mediated by activated oxygen generated from the iron complex in its chelator moiety. Spin-offs from this moiety, HPH-1Trt and HPH-2Trt, with anti-cancer activities were recently synthesized. In this paper, we developed inhibitors of NAD-dependent deacetylase isoform 2 of Sirtuin protein (SIRT2), based on HPH-1Trt/HPH-2Trt, and aimed to generate new anti-cancer drugs. HPH-1Trt and HPH-2Trt had in vitro anti-SIRT2 inhibitory activity with 50% inhibitory concentration (IC50) values of 5.5 and 8.8 μM, resp. A structural portion of HPH-1Trt/HPH-2Trt, a tritylhistidine derivative TH-1, had stronger activity (IC50 = 1.7 μM), and thus, fourteen derivatives of TH-1 were synthesized. Among them, TH-3 had the strongest activity (IC50 = 1.3 μM). Selective binding of TH-3 in the pocket of SIRT2 protein was confirmed with a mol. docking study. Furthermore, TH-3 strongly lowered viability of the breast cancer cell line MCF7 with an IC50 of 0.71 μM. A structure-activity relationship study using cell lines suggested that the mechanism of TH-3 to suppress MCF7 cells involves not only SIRT2 inhibition, but also another function. This compound may be a new candidate anti-cancer drug.
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