New 3 ‐Substituted‐2‐(4‐hydroxyanilino)pyridine Derivatives: Synthesis, Antitumor Activity, and Tubulin Polymerization Inhibition

A series of new pyridine derivatives 4a–c, 5a–d, 6a–d, 7a–f, and 8a–f structurally related to ABT‐751 were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were tested for their cytotoxic activity in vitro against the HCT‐116 and HepG‐2 cancer cell lines using the MTT assay. The results showed that compound 8d has higher cytotoxic activity than the reference antimitotic agent colchicine, against both tested cell lines, with IC50 = 0.52 and 1.40 μM, respectively. The three most active compounds, 5d, 8b, and 8d, were further screened in vitro for inhibition of tubulin and showed remarkable results in comparison to colchicine. 4‐{3‐[5‐(4‐Methoxyphenylamino)‐1,3,4‐oxadiazol‐2‐yl]‐pyridin‐2‐ylamino}phenol (8d) was designed based on the potent cytotoxic and tubulin inhibitory activities displayed by ABT‐751 and IMC‐038525. Compound 8d exhibited potent cytotoxic activity against HCT‐116 and HepG‐2 cells with IC50 values of 0.52 and 1.40 µM, respectively. It also displayed considerable tubulin inhibitory activity: 92.60 and 93.20% against HCT‐116 and HepG‐2 cells, respectively.
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research