Synthesis and evaluation of novel benzophenone-thiazole derivatives as potent VEGF-A inhibitors.

A series of 2-(4-benzoyl-phenoxy)-N-(4-phenyl-thiazol-2-yl)-acetamides (10a-n) were synthesized by multistep reaction sequence and all the compounds were well characterized for structural elucidation. The in vitro cytotoxicity of compounds 10a-n was evaluated against EAC and DLA cell lines using trypan blue dye exclusion method. Further MTT assay and LDH release assay, followed by in vivo studies on murine model were also evaluated. The compound 10h with a methyl and fluoro groups at benzophenone moiety and methoxy group at phenyl ring was in a leading position to exhibit the promising antiproliferative effect through translational VEGF-A inhibition.

DAO-9 (2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole) exhibits p53 induced apoptogenesis through caspase-3 mediated endonuclease activity in murine carcinoma.

One of the main strategies to inhibit the tumor growth is to promote the biochemical events leading to DNA degradation, which would eventually culminate in apoptosis. We have earlier reported that the 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole(DAO-9) possessed anti-cancer activity. To address the exact molecular mechanism underlying anti-cancer property, present study focused on evaluating the anti-tumor effect of the DAO-9 on murine ascites carcinoma cells using various in vivo and in vitro assays. The in vivo assays implicated a strong regression in tumor growth of ascites carcinoma after treatment which is due to apoptogenic efficacy as assessed through structural morphology of EAC cells by Giemsa, Acridine orange, Annexin V staining and FACS analysis. Nucleosomal DNA fragmentation induced by DAO-9 is due to activation of caspase-3 mediated DNAse as verified by endonuclease assays and immunoblot analysis. The caspase-3 activation mechanism is by induction of intrinsic cascade signaling molecules, such as p53, Bax, Bad and cytochrome c (cyt c) expression as verified by western blot. The results concluded that the tumor inhibiting activity of DAO-9 is due to activation of the apoptotic signaling cascade, which could be translated into targeted anti-cancer drug in the near future.

Synthesis, characterization, biological and catalytic applications of transition metal complexes derived from Schiff base.

A novel series of Cu(II), Ni(II), Zn(II), Co(II), and Cd(II) complexes have been synthesized from the Schiff base. Structural features were determined by analytical and spectral techniques like IR, (1)H NMR, UV-vis, elemental analysis, molar electric conductibility, magnetic susceptibility and thermal studies. The complexes are found to be soluble in dimethylformamide and dimethylsulfoxide. Molar conductance values in dimethylformamide indicate the non-electrolytic nature of the complexes. Binding of synthesized complexes with calf thymus DNA (CT DNA) was studied. There is significant binding of DNA in lanes 2, 3, and 5. Lanes 4 and 6 are showing more florescence when compared to the control indicating that these molecules are strongly bound to the DNA by inserting themselves between the two stacked base pairs and exhibiting their original property of fluorescence. Angiogenesis study has revealed that the compounds B-2, B-4 and B-5 have potent antitumor efficacy and activation of antiangiogenesis could be one of the possible underlying mechanisms of tumor inhibition.

(4-Fluoro-phen-yl)(2-hy-droxy-5-methyl-phen-yl)methanone.

In the title compound, C14H11FO2, the dihedral angles beteen the central C3O ketone residue and the fluoro- and hy-droxy-substituted benzene rings are 50.44 (9) and 12.63 (10)°, respectively. The planes of the benzene rings subtend a dihedral angle of 58.88 (9)° and an intra-molecular O-H⋯O hydrogen bond closes an S(6) ring. No directional inter-actions beyond van der Waals packing contacts were identified in the crystal structure.

(4-Fluoro-phen-yl)(4-hy-droxy-3-methyl-phen-yl)methanone.

In the title compound, C14H11FO2, the two benzene rings are not coplanar, with a dihedral angle of 57.45 (12)° between their planes. In the crystal, mol-ecules are linked by an O-H⋯O hydrogen bond, forming a 21 helical chain along the b axis.

Synthesis and tumor inhibitory activity of novel coumarin analogs targeting angiogenesis and apoptosis.

A sequence of coumarin analogs 5a-j was obtained by multi step synthesis from hydroxy benzophenones (1a-j). The in vitro antiproliferative effect of the title compounds was tested against Ehrlich ascites carcinoma (EAC) and Daltons lymphoma ascites (DLA) cell lines. Among the series, compound 5c with bromo group in the benzophenone moiety was endowed with excellent antiproliferative potency with significant IC50 value. Further, in vivo antitumor effect of compound 5c against murine EAC and solid DL tumor model system was evident by the extended survivality. The tumor inhibitory mechanism of compound 5c was due to the antiangiogenesis and promotion of apoptosis. These results suggest possible applications of compound 5c which could be developed as a potent anticancer drug in the near future.

Synthesis and evaluation of in vitro antioxidant properties of novel 2,5-disubstituted 1,3,4-oxadiazoles.

2,5-Disubstituted 1,3,4-oxadiazole compounds are one of the most attractive heterocyclic compounds for researchers due to their biological activities. In the undertaken research, a number of potential 2,5-disubstituted 1,3,4-oxadiazole analogues were synthesized through multi step reaction and characterized by FT-IR, 1H NMR, mass spectra, and also by elemental analysis. Further benzophenone tagged indole acetohydrazides and 2,5-disubstituted 1,3,4-oxadiazoles were evaluated for antioxidant potential, through different in vitro models such as DPPH, nitric oxide and hydrogen peroxide methods. In the series of compounds some of them had shown good to moderate in vitro antioxidant potential compare to the standard drug ascorbic acid in all the above three methods.

(4-Hy-droxy-3-methyl-phen-yl)(phen-yl)methanone.

In the title compound, C14H12O2, the benzene rings make a dihedral angle of 58.84 (12)°. In the crystal, mol-ecules are linked into chains along the b-axis direction by O-H⋯O hydrogen bonds. These chains are further linked by C-H⋯O hydrogen bonds, forming layers parallel to the bc plane.

Design, synthesis, and anticancer properties of novel benzophenone-conjugated coumarin analogs.

In the current scenario, development of anticancer drugs with specific targets is of prime importance in modern chemical biology. Observing the importance of benzophenone and coumarin nucleus, it would be worthwhile to design and synthesize novel benzophenone derivatives (8a-o) bearing the coumarin nucleus. Further, they were screened for prospective anticancer activities in vitro against the Michigan Cancer Foundation-7 (MCF-7) and Ehrlich's ascites tumor (EAT) cell lines and their biomarkers, followed by in silico studies regarding phosphoinositide 3-kinase (PI3K) and caspase by molecular docking. Benzophenones have been reported as potential drugs targeting tumor angiogenesis; thus, the formation of neovessels in an in vivo model system like CAM, which is angiogenesis dependent, was observed in the presence of compounds 8a-o. The above findings would help in understanding their putative potential as therapeutic agents for cancer patients.