Molecular docking study, synthesis and biological evaluation of Schiff bases as Hsp90 inhibitors.
Heat shock protein 90 (Hsp90) is an emerging attractive target for the discovery of novel cancer therapeutic agents. Docking methods are powerful in silico tools for lead generation and optimization. In our mission to rationally develop novel effective small molecules against Hsp90, we predicted the potency of our designed compounds by Sybyl surflex Geom X docking method. The results of the above studies revealed that Schiff bases derived from 2,4-dihydroxy benzaldehyde/5-chloro-2,4-dihydroxy benzaldehyde demonstrated effective binding with the protein. Subsequently, a few of them were synthesized (1-10) and characterized by IR, (1)HNMR and mass spectral analysis. The synthesized molecules were evaluated for their potential to suppress Hsp90 ATPase activity by Malachite green assay. The anticancer studies were performed by 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The software generated results was in satisfactory agreement with the evaluated biological activity.
Department of Pharmaceutical Chemistry, Gokaraju Rangaraju College of Pharmacy, Osmania University, Bachupally, Hyderabad, India; R&D centre, Department of Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Hyderabad, India. Electronic address: sayandg@rediffmail.com.
Sayan
S
Dutta Gupta
Department of Pharmaceutical Chemistry, Gokaraju Rangaraju College of Pharmacy, Osmania University, Bachupally, Hyderabad, India.
D
D
Snigdha
Department of Biological Chemistry, Faculty of Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina.
Gisela I
GI
Mazaira
Department of Biological Chemistry, Faculty of Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina; Institute of Experimental Biology and Medicine-CONICET, Buenos Aires, Argentina.
Mario D
MD
Galigniana
Department of Pharmaceutical Chemistry, Gokaraju Rangaraju College of Pharmacy, Osmania University, Bachupally, Hyderabad, India.
C V S
CV
Subrahmanyam
Swami Vivekananda Institute of Pharmaceutical Sciences, Nalgonda, Andhrapradesh, India.
N L
NL
Gowrishankar
Department of Pharmaceutical Chemistry, Gokaraju Rangaraju College of Pharmacy, Osmania University, Bachupally, Hyderabad, India.
N M
NM
Raghavendra
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011485:Protein Binding; D012545:Schiff Bases / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D012545:Schiff Bases
Docking; Hsp90; MTT; Malachite green; Schiff bases