2,4-dihydroxy benzaldehyde derived Schiff bases as small molecule Hsp90 inhibitors: rational identification of a new anticancer lead

Hsp90 is a molecular chaperone that heals diverse array of biomolecules ranging from multiple oncogenic proteins to the ones responsible for development of resistance to chemotherapeutic agents. Moreover they are over-expressed in cancer cells as a complex with co-chaperones and under-expressed in normal cells as a single free entity. Hence inhibitors of Hsp90 will be more effective and selective in destroying cancer cells with minimum chances of acquiring resistance to them. In continuation of our goal to rationally develop effective small molecule azomethines against Hsp90, we designed few more compounds belonging to the class of 2,4-dihydroxy benzaldehyde derived imines (1-13) with our validated docking protocol. The molecules exhibiting good docking score were synthesized and their structures were confirmed by IR, (1)H NMR and mass spectral analysis. Subsequently, they were evaluated for their potential to suppress Hsp90 ATPase activity by Malachite green assay. The antiproliferative effect of the molecules were examined on PC3 prostate cancer cell lines by adopting 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay methodology. Finally, schiff base 13 emerged as the lead molecule for future design and development of Hsp90 inhibitors as anticancer agents.Fil: Dutta Gupta, Sayan. Osmania University; India. Jawaharlal Nehru Technological University; IndiaFil: Revathi, B.. Osmania University; IndiaFil: Mazaira, Gisela Ileana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Subrahmanyam, C. V. S.. Osmania University; IndiaFil: Gowrishankar, N. L.. Swami Vivekananda Institute of Pharmaceutical Sciences; IndiaFil: Raghavendra, N. M.. Osmania University; Indi

Anti-Diabetic Potential of Aqueous, Methanolic and Saponin Extract of Leaves of Ziziphus nummlaria Linn.

The aqueous and methanolic extract of the leaves of Zizyphus nummularia were obtained from successive solvent extraction. The methanolic extract was further solvent extracted with water saturated n-butanol solvent and organic layer was acidified with 1 N KOH to obtain the raw saponin extract. Different concentrations of extracts were treated with alpha amylase enzyme in phosphate buffer (pH 6.9), their spectroscopic estimation was done at 540 nm after stopping the reaction with DNS. All the extracts have produced significant enzyme inhibition and their IC50 value was observed to be 114.16 µg/ml ± 1.30 to 137.87 µg/ml ± 1.82.Â

Chloridobis[diphenyl­glyoximato(1–)-κ2 N,N′](1H-imidazole-κN 3)cobalt(III) hemihydrate

The Co centre in the title compound, [Co(C14H11N2O2)2Cl(C3H4N2)]·0.5H2O, shows a slightly distorted octa­hedral coordination geometry. The glyoximate units of the mol­ecule are linked by O—H⋯O hydrogen bonds with the H atom almost in the middle of the two O atoms. The crystal packing is stabilized through inter­molecular N—H⋯O, N—H⋯N and O—H⋯Cl hydrogen bonds. The uncoordinated water mol­ecule shows half-occupation

4-[(4′-Chloro­methyl-[1,1′-biphen­yl]-4-yl)meth­yl]bis­(dimethyl­glyoximato-κ2 N,N′)(pyridine-κN)cobalt(III)1

The title compound, [Co(C14H14Cl)(C4H6N2O2)2(C5H5N)], is a model compound for the more complex cobalamines like vitamins B12. The CoIII atom is coordinated by a (4′-chloro­methyl-[1,1′-biphen­yl]-4-yl)methyl group, an N-bonded pyridine and two N,N′-bidentate dimethyl­glyoximate ligands in a distorted octa­hedral geometry. The glyoximate ligands exhibit intra­molecular O—H⋯O hydrogen bonds, which is very common in cobaloxime derivatives

Dichlorido(dimethyl­glyoximato-κ2 N,N′)(dimethyl­glyoxime-κ2 N,N′)cobalt(III)

In the title compound, [Co(C4H7N2O2)Cl2(C4H8N2O2)], the CoIII ion has a distorted octa­hedral coordination environment. The equatorial plane consists of four N atoms, two each from the dimethyl­glyoxime and dimethyl­glyoximate ligands, while the two axial positions are occupied by two chloride ions. Strong intra­molecular O—H⋯O hydrogen bonds are observed between the dimethyl­glyoxime and dimethyl­glyoximate ligands. Mol­ecules are linked into a chain running along the [101] direction by O—H⋯O and C—H⋯Cl hydrogen bonds. The chains are cross-linked through inter­molecular C—H⋯Cl hydrogen bonds