Microwave-assisted one pot synthesis, characterization, biological evaluation and molecular docking studies of steroidal thiazoles.

In the present manuscript, a series of steroidal thiazole derivatives (4-6, 8) have been synthesized in efficient manner by one step reaction methodology employing microwave irradiation. The synthesis involves the reaction of steroidal ketones (1-3, 7) with thiosemicarbazide and phenacyl bromide. Structural assignment of the products was confirmed on the basis of IR, 1H NMR, 13C NMR, MS and analytical data. The synthesized compounds were screened for in vitro antioxidant activity by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. In addition, the products 4-6, 8 were also tested for pBR322 DNA cleavage activity, genotoxicity, reactive oxygen species (ROS) production and RBC hemolysis. Molecular docking analysis was carried out to validate the specific binding mode of the newly synthesized compounds into the active site of DNA. Docking showed formation of more stable complexes of compounds 4 and 8 with the free binding energies -8.1 and -8kcal/mol, respectively. Hence, it could be suggested that the steroidal compounds bearing a core thiazole scaffold would be a potent biological agent.

Neurodegenerative diseases linked to misfolded proteins and their therapeutic approaches: A review.

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, Creutzfeldt-Jacob, Huntington's diseases and amyotrophic lateral sclerosis, are mainly characterized by the massive deposition of misfolded protein aggregates consequent to aberrant production or overexpression of specific proteins. The development of new therapeutics for the treatment of neurodegenerative pathophysiologies currently stands at a crossroads. This presents an opportunity to transition future drug discovery efforts to target disease modification, an area in which much still remains unknown. In this review we examine recent progress in the area of neurodegenerative drug discovery, focusing on some of the most common targets.

Bioactive Benzofuran derivatives: A review.

In nature's collection of biologically active heterocycles, benzofuran derivatives constitute a major group. The broad spectrum of pharmacological activity in individual benzofurans indicates that this series of compounds is of an undoubted interest. Benzofuran and its derivatives have attracted medicinal chemists and pharmacologists due to their pronounced biological activities and their potential applications as pharmacological agents. Due to the wide range of biological activities of benzofurans, their structure activity relationships have generated interest among medicinal chemists, and this has culminated in the discovery of several lead molecules in numerous disease conditions. The outstanding development of benzofuran derivatives in diverse diseases in very short span of time proves its magnitude for medicinal chemistry research. The present review is endeavour to highlight the progress in the various pharmacological activities of benzofuran derivatives in the current literature with an update of recent research findings on this nucleus.

Synthesis and anti-tumor evaluation of B-ring substituted steroidal pyrazoline derivatives.

The synthesis and anti-tumor activity screening of new steroidal derivatives (4-18) containing pharmacologically attractive pyrazoline moieties are performed. During in vitro anticancer evaluation, the newly synthesized compounds displayed moderate to good cytotoxicity on cervical and leukemia cancer cell lines. In addition these compounds were found to be nontoxic to normal cell (PBMCs) (IC50>50 µM). The structure-activity relationship is also discussed. The most effective anticancer compound 9 was found to be active with IC50 value of 10.6 µM. It demonstrated significant antiproliferative influence on Jurkat cell lines. The morphological changes and growth characteristics of HeLa cells treated with compound 4 were analyzed by means of SEM.

6-Hy-droxy-imino-5α-cholestane.

The title compound, C(27)H(47)NO, is a steroid derivative composed of a saturated carbon fused-ring framework with an alkyl side chain. Ring bond lengths have normal values with an average of 1.533 (2) Å, while the cholestane side chain shows an average bond length of 1.533 (2) Å. The three cyclohexane rings adopt chair conformations or close to chair conformations while the cyclopentane ring is twisted. The cholesterol side-chain is fully extended with a gauche-trans conformation of the terminal methyl groups. There are eight chiral centres in the molecule; the absolute configuration of these sites was determined from the structure presented. There are two molecules in the asymmetric unit; in one, the alkyl chain is disordered over two sets of sites [occupancy ratios of 0.50:0.50 and 0.67:0.33].