Synthesis, Characterization, Bioevaluation, and Docking Studies of Spiroisatin‐based Hydrazide Conjugates

A series of spiroisatin‐based hydrazide conjugates IV(a–t) were synthesized and structurally characterized using spectral data, with compound IV‐a further confirmed by X‐ray diffraction analysis. All the synthesized compounds were evaluated for their biological potential in a cell‐painting assay. Among the synthesized spiroisatin derivatives, compound IV‐p exhibited significant activity in inducing cellular morphological changes, with induction value of 30.6%. Additionally, some compounds showed high biosimilarities with marketed drugs. Specifically, the compounds IV‐n and IV‐p showed a high biosimilarity with the orally active iron chelator deferasirox, and IV‐m showed high a biosimilarity with the kinase inhibitor alisertib. Furthermore, compounds IV‐p showed significant inhibition against human breast cancer (MDA‐MB‐231= 82.37%) and colorectal carcinoma cell lines (HCT‐116 =86.25%) during preliminary investigations. Moreover, it was revealed through molecular docking analysis that IV‐p possess a good binding score against ferroportin and Aurora A kinase (‐9.3 kcal/mol and ‐9.2 kcal/mol) which are quite comparable with the deferasirox (‐9.2 kcal/mol) and alisertib (‐9.8 kcal/mol). Pharmacokinetic studies revealed that the synthesized conjugates have good oral bioavailability, balanced hydrophilicity and minimal toxicity. The results of this study clearly highlight the potential of these conjugates as promising small bioactive molecules.