Herein, we synthesized some new imidazole‐tetrazole‐amide hybrids (7 a–o) and investigated their antiproliferative activity on three human cancer cell lines like HEPG2, A549 and MCF‐7. Generally, most of them displayed more activity on A549 than other two cell lines. Specifically, compounds N‐(3,5‐dimethoxyphenyl)‐2‐(5‐(1‐methyl‐1H‐imidazol‐2‐yl)‐2H‐tetrazol‐2‐yl)acetamide (7 b) and N‐(4‐chloro‐3,5‐dimethoxyphenyl)‐2‐(5‐(1‐methyl‐1H‐imidazol‐2‐yl)‐2H‐tetrazol‐2‐yl)acetamide (7 m) had almost similar potency on A549, while, they had significant activity on MCF‐7 in comparison to the standard drug Combretastatin A‐4 (CA‐4). Besides, compounds 4‐(2‐(5‐(1‐methyl‐1H‐imidazol‐2‐yl)‐2H‐tetrazol‐2‐yl)acetyl)benzonitrile (7 j) and N‐(3,5‐dichlorophenyl)‐2‐(5‐(1‐methyl‐1H‐imidazol‐2‐yl)‐2H‐tetrazol‐2‐yl)acetamide (7 k) showed most promising activity against A549 as compared to the CA‐4. The uppermost activity against A549 found for the compounds 7 j and 7 m have IC50 values 1.09 and 1.26 μM respectively. The ability of potent compounds 7 b, 7 j, 7 k and 7 m to inhibit the tubulin polymerization was then studied and found that compounds 7 b and 7 m exhibited promising potency in comparison to the CA‐4. Further, molecular docking studies of compounds 7 b, 7 j, 7 k and 7 m into the tubulin's colchicine‐binding site revealed the possible interactions with tubulin. Finally, in silico ADMET studies revealed that compounds 7 b, 7 j, 7 k and 7 m showed high GI absorption and followed rules of Lipinski, Ghose, Veber, Egan and Muegge without any deviation. Further anticancer mechanism studies are under progress.

The synthesis of some new quinoline‐thiazolidine‐2,4‐dione coupled pyrazoles (7 a–7 n) via Knoevengal condensation, N‐alkynylation and tandem one‐pot Sonogashira coupling‐cyclocondensation paths was described. All the compounds were further evaluated for their in vitro anti‐breast cancer activity against MDA‐MB‐231 and MCF‐7 and results were compared with standard drug erlotinib. Most of analogues were potent against MCF‐7 than the MDA‐MB‐231. In specific, compounds (Z)‐3‐((3‐(4‐methoxyphenyl)‐1H‐pyrazol‐5‐yl)methyl)‐5‐(quinolin‐4‐ylmethylene) thiazolidine‐2,4‐dione (7 d) and (Z)‐5‐(5‐((2,4‐dioxo‐5‐(quinolin‐4‐ylmethylene)thiazolidin‐3‐yl)methyl)‐1H‐pyrazol‐3‐yl)isophthalonitrile (7 m) had superior potency against MCF‐7 and MDA‐MB‐231 with IC50 (μg/mL) values ranging from 2.13 to 6.07. Besides, compounds (Z)‐3‐((3‐(3,5‐dimethoxyphenyl)‐1H‐pyrazol‐5‐yl)methyl)‐5‐(quinolin‐4ylmethylene)thiazolidine‐2,4‐dione (7 e), (Z)‐3‐((3‐(4‐chlorophenyl)‐1H‐pyrazol‐5‐yl)methyl)‐5‐(quinolin‐4‐ylmethylene)thiazolidine‐2,4‐dione (7 h), (Z)‐4‐(5‐((2,4‐dioxo‐5‐(quinolin‐4‐ylmethylene)thiazolidin‐3‐yl)methyl)‐1H‐pyrazol‐3‐yl)benzonitrile (7 i) and (Z)‐3‐((3‐(4‐nitrophenyl)‐1H‐pyrazol‐5‐yl)methyl)‐5‐(quinolin‐4‐ylmethylene)thiazolidine‐2,4‐dione (7 j) showed most promising potency against MCF‐7 with IC50 values 5.97‐6.43 μg/mL. The ability of compounds 7 d, 7 e, 7 h, 7 i, 7 j and 7 m to inhibit EGFR tyrosine kinase was also studied and found that compounds 7 d and 7 m showed remarkable potency as compared to erlotinib with inhibition 87.6 % and 91.4 % respectively. Molecular docking studies were then carried out for most potent compounds 7 d, 7 i, and 7 m and erlotinib on EGFR, and these compounds had encouraging binding energies and inhibition constants in comparison to erlotinib. Finally, compounds 7 d, 7 i and 7 m have high intestinal absorption with Caco‐2 permeability and followed Lipinski rules without any deviation.