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The antitumor activity of the newly synthesized 5-arylidenethiazolidine-2,4-dione derivatives 18a-f and 19a-f was investigated, compared to doxorubicin (IC 50  = 4.17-8.87 μM) and SAHA (IC 50  = 2.70-7.11 μM). Among the tested molecules, compounds 18b, 18c, 18f, 19d, and 19e displayed the highest antitumor activity against cancer cell lines (IC 50  = 3.16-28.94 μM). Further, compounds 18b, 18c, 18f, and 19d were tested as Histone deacetylases (HDACs) inhibitors compared with Entinostat (IC 50  = 0.093-0.75 μM). Compounds 18b, 18c, 18f, and 19d inhibited HDAC1, HDAC2, HDAC8, and HDAC6 enzymes with IC 50 values ranging from 0.144 to 1.741 μM. In addition, compound 18b caused apoptosis via a mitochondrial-mediated pathway and led to cell cycle arrest at the G1 phase. It also increased caspases-3 and caspases-7 by 5.2-3.9 and 9.1-3.7 folds, respectively. The molecular docking analysis of compounds 18b and 18c revealed that they could bind to the active sites of HDAC1, HDAC2, HDAC8, and HDAC6 like co-crystallized inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Human carbonic anhydrase (CA, EC 4.2.1.1) (hCA) isoforms I, II, IX, and XII were investigated for their inhibitory activity with a series of new Schiff's bases based on quinazoline scaffold 4 - 27 . The hCA I isoform was efficiently inhibited by Schiff's bases 4 - 6 , 10 - 19 , 22 - 27 and had an inhibition constant (Ki) value of 52.8-991.7 nM compared with AAZ (Ki, 250 nM). Amongst the quinazoline derivatives, the compounds 2 , 3 , 4 , 10 , 11 , 16 , 18 , 24 , 26 , and 27 were proven to be effective hCA II inhibitors, with Ki values of 10.8-52.6 nM, measuring up to AAZ (Ki, 12 nM). Compounds 2 - 27 revealed compelling hCA IX inhibitory interest with Ki values of 10.5-99.6 nM, rivaling AAZ (Ki, 25.0 nM). Quinazoline derivatives 3 , 10 , 11 , 13 , 15 - 19 , and 24 possessed potent hCA XII inhibitory activities with K I values of 5.4-25.5 nM vs. 5.7 nM of AAZ. Schiff's bases 7 , 8 , 9 , and 21 represented attractive antitumor hCA IX carbonic anhydrase inhibitors (CAIs) with K I rates (22.0, 34.8, 49.2, and 45.3 nM, respectively). Compounds 5 , 7 , 8 , 9 , 14 , 18 , 19 , and 21 showed hCA I inhibitors on hCA IX with a selectivity index of 22.46-107, while derivatives 12 , 14 , and 18 showed selective hCA I inhibitors on hCA XII with a selectivity profile of 45.04-58.58, in contrast to AAZ (SI, 10.0 and 43.86). Compounds 2 , 5 , 7 - 14 , 19 - 23 , and 25 showed a selectivity profile for hCA II inhibitors over hCA IX with a selectivity index of 2.02-19.67, whereas derivatives 5 , 7 , 8 , 13 , 14 , 15 , 17 , 20 , 21 , and 22 showed selective hCA II inhibitors on hCA XII with a selectivity profile of 4.84-26.60 balanced to AAZ (SI, 0.48 and 2.10).