Design, synthesis, in vitro and in silico bioactivity profiles of new urea/thiourea derivatives of 2-pyridyl piperazine as potent antioxidant and antimicrobial agents: chemo-bio-computational approach.

Synthesis of a series of new urea and thiourea derivatives of 2-pyridyl piperazine was accomplished by reacting various isocyanates and isothiocyanates in the presence of triethylamine (TEA) at 50 °C. All the title compounds were obtained in high yields and their structures were characterized by IR, 1H, 13C NMR, Mass spectral, and Elemental analysis. The synthesized compounds were screened for in vitro and in silico antioxidant and antimicrobial activities. All the title compounds exhibited potent antioxidant and antimicrobial activities. Out of all, 2c and 2f against DPPH, H2O2 and Nitro oxide have exhibited significant activity and the levels of activity were higher than the reference compounds, ascorbic acid and BHT. Whereas 2a, 2c, 2f and 2j have shown prominent activity in terms of zone of inhibition against all the microbial strains tested than the standards such as levofloxacin and nystatin. In addition in silico studies also conveyed the same that is 2a, 2c, 2f and 2j have displayed the highest binding energies against peroxiredoxins and DNA gyrase protein than the standards akin to the rest of the compounds. In overall, 2c and 2f have exhibited most promising antioxidant and antimicrobial activity than the rest of the title compounds in vitro and in silico. Hence, 2c and 2f will stand as a lead and promising antioxidant and antimicrobial drug candidates in future.Communicated by Ramaswamy H. Sarma.

Antiepileptic potential of Bacopa monnieri in the rat brain during PTZ-induced epilepsy with reference to cholinergic system and ATPases.

Epilepsy is a chronic central nervous system disorder that occurs not only with the imbalance of glutamatergic neurons and inhibitory gamma-aminobutyric acid (γ-GABA) neurons, but also with abnormal Central cholinergic neuronal regulation. Since long term usage of antiepileptic drugs cause high incidence of pharmacoresistance and untoward side effects, attention has been paid in recent years to screen bioactive compounds from natural medicinal plants for the treatment of several neurological disorders including Epilepsy. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-convulsant effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurvedic treatments related to neurological complications. The present study is designed to assess the neurotoxicity of Pentylene tetrazole (PTZ), an epileptic compound with particular reference to Cholinergic system and ATPases in different brain regions of rat to explore the possible antiepileptic effect of different extracts of BM in comparison with Diazepam (DZ) (Reference control). The activity levels of Acetyl cholinesterase (AChE) and ATPases were decreased in different regions of brain during PTZ induced epilepsy which were increased in epileptic rats pretreated with different extracts of Bacopa monnieri except EAE and AE. In addition Acetylcholine (ACh), levels were increased during PTZ induced epilepsy when compared with normal control and levels were reversed on pretreatment with different extracts of BM. Recoveries of these parameters suggest that the bioactive factors present in the extracts offer neuroprotection by interrupting the pathological cascade that occurs during epileptogenesis.

Design, synthesis, characterization and in vitro, in vivo and in silico antimicrobial and antiinflammatory activities of a new series of sulphonamide and carbamate derivatives of a nebivolol intermediate.

A series of new sulphonamide and carbamate derivatives of Nebivolol drug intermediate (5) were designed and synthesized by reacting various biopotent sulphonylchlorides and chloroformates. The synthesized compounds are structurally characterized by spectral (IR, 1H & 13C NMR and mass) and screened for their in vitro antimicrobial activity against four bacterial and three fungal strains, in vitro and in vivo antiinflammatory activity against LPS-induced inflammation in RAW 264.7, in vitro COX-1 and COX-2 inhibition potentiality, antagonistic profiles of carrageenan induced paw edema and cotton pellet induced granuloma in rat. Further, the compounds were screened for their antimicrobial and antiinflammatory activity against DNA gyrase A, COX-1 and COX-2 by using molecular docking approach. The bioactivity and toxicity risks were analysed through Molecular Operating Environment. The results revealed that the compounds 8b, 8c, 8d, 8e, 8f, 8g and 9a exhibited the most promising antimicrobial activity against all the bacterial and fungal strains tested when compared with the standard drugs streptomycin and fluconazole. In view of in antiinflammatory activity, the compounds, 8b, 8c, 8d, 8e, 8f, 8g and 9a have shown potent antiinflammatory activity by inhibiting the LPS-induced inflammation in RAW 264.7 cell line, concentration dependent inhibition of COX-1 and COX-2, dose response dependent antagonism of carrageenan induced paw edema and granuloma tissue in rat. Molecular docking, ADMET and QSAR studies predicted that the recorded in silico profiles are in strong correlation with in vitro and in vivo antimicrobial and antiinflammatory results. In addition, the elevated toxicology risks of the title compounds are identified with in the potential limits of drug candidates. Hence, it is suggested that the synthesized derivatives will stand as the promising antimicrobial and anti-inflammatory drug candidates in future.