Background: Heat shock protein 90 (Hsp90) is an encouraging anticancer target for the development
of clinically significant molecules. Schiff bases play a crucial role in anticancer research because of their ease of
synthesis and excellent antiproliferative effect against multiple cancer cell lines. Therefore, we started our research
work with the discovery of resorcinol/4-chloro resorcinol derived Schiff bases as Hsp90 inhibitors, which
resulted in the discovery of a viable anticancer lead molecule.
Objective: The objective of the study is to discover more promising lead molecules using our previously established
drug discovery program, wherein the rational drug design is achieved by molecular docking studies.
Methods: The docking studies were carried out by using Surflex Geom X programme of Sybyl X-1.2 version
software. The molecules with good docking scores were synthesized and their structures were confirmed by IR,
1H NMR and mass spectral analysis. Subsequently, the molecules were evaluated for their potential to attenuate
Hsp90 ATPase activity by Malachite green assay. The anticancer effect of the molecules was examined on PC3
prostate cancer cell lines by utilizing 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)
Results: Schiff bases 11, 12, 20, 23 and 27 exhibiting IC50 value below 1μM and 15μM, in malachite green
assay and MTT assay, respectively, emerged as viable lead molecules for future optimization.
Conclusion: The research work will pave the way for the rational development of cost-effective Schiff bases as
Hsp90 inhibitors as the method employed for the synthesis of the molecules is simple, economic and facile.