Compounds containing both thiazole and arylsulfone moieties are recognized for their high biological activity and ability to fight a variety of ailments. Thus, in this context, new derivatives of (thiazol-2-yl)hydrazone with an arylsulfone moiety were synthesized as CPTH2 analogs with potent anti-histone lysine acetyl-transferase activity. Compounds 3, 4, 10b, and 11b showed an excellent inhibitory effect on P300 (E1A-associated protein p300), compared to CPTH2. Among all the tested derivatives, compound 10b revealed the highest activity against both P300 and pCAF. In addition, the new hits were tested for anticancer efficacy against two leukemia cell lines. Most of them showed a moderate to potent antitumor effect on the k562 and CCRF-CEM cell lines. Interestingly, the activity of compound 10b against the k562 cell line was found to be higher than that of CPTH2. Furthermore, it showed a good safety profile, better than CPTH2 on normal cells. Molecular docking analysis was carried out to reveal the crucial binding contacts in the inhibition of the P300 and pCAF enzymes.
Keywords: CPTH2 analogs; anti-HAT activity; aryl sulfonyl acetophenone; thiazoles; thiosemicarbazone.
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