Anticancer 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones as tubulin inhibitors

Abstract

Studying the anticancer activity of 5-arylidene-2-(4-hydroxyphenyl)aminothiazol-4(5H)-ones towards cell lines of different cancer types allowed the identification of hit-compounds inhibiting the growth of daunorubicin-(CEM-DNR, IC 50 = 0.32-1.28 µM) and paclitaxel-resistant (K562-TAX, IC 50 = 0.21-1.23 µM) cell lines, with favorable therapeutic indexes. The studied compounds induced apoptosis and cellular proliferation in treated CCRF-CEM cells. The hit compounds were shown to induce mitotic arrest by interacting with tubulin, inhibiting its polymerization by binding to the colchicine binding site.

The design, synthesis, biological evaluation, and molecular docking of new 5‐aminosalicylamide‐4‐thiazolinone hybrids as anticancer agents

“…clearly reveal that the arylidene moiety is essential for the antitumor activity. This is because 5-unsubstituted-4-thiazolinones (15)(16)(17)(18)(19)(20) and 5-methyl-4-thiazolinones (21 and 22) showed no antiproliferative activity against any of the tested cell lines. When 15-20 reacted with aromatic benzaldehydes and cinnamaldehyde forming derivatives substituted at position 5 with arylidene, however, such derivatives (23)(24)(25)(26)(27)(28) showed antiproliferative activity.…”

“…This could be attributed to the steric effect as they are 2ry alkyl chlorides which impair the cyclization process. The cyclized products (15)(16)(17)(18)(19)(20)(21)(22) were collected and washed with water to get analytically pure products.…”

“…[14] Among 4-thiazolidinones, 5-arylidene-2-arylamino-4-thiazolidinones are of special interest as one of the most perspective groups in the recent anticancer drug discovery process. [11,14,15] On the other hand, abundant research has demonstrated that 5-ASA and some of its derivatives (Figure 1) exhibited anticancer activities through cyclooxygenase-2-dependent and -independent mechanisms. [16][17][18][19][20][21][22][23][24][25] Of these derivatives 5-ASA esters or amides and 5-amino derivatives were synthesized as lavendustin A analogs.…”

“…General procedure for the synthesis of N-(substituted)−2-hydroxy-5-[(4-oxo-4, 5-dihydrothiazol-2 yl)amino]benzamide(15)(16)(17)(18)(19)(20)(21)(22) …”