Computational Design of Plant-Based Antistress Agents Targeting Nociceptin Receptor.

Stress is the body's reaction to the challenges it faces, and it produces a multitude of chemical molecules known as stressors as a result of these reactions. It's also a misalignment of the sympathetic and parasympathetic nervous systems causing changes in a variety of physiological reactions and perhaps leading to stress disorders. The reduction in neurotransmitter & neurohormonal hormones is mainly governed by the nociceptin receptor as G-protein coupled receptor and increased the level of reactive oxygen species. Various synthetic medicines that target nociceptin receptors were utilized to reduce the effects of stress but they come up with a variety of side effects. Because of the widespread utilization and renewed interest in medicinal herbal plants considered to be alternative antistress therapy. Our present work is an approach to decipher the molecular nature of novel herbal leads by targeting nociceptin receptor, under which herbal compounds were screened and validated through in-silico methods. Among screened leads, withanolide-B showed stable association in the active site of the nociceptin receptor as an antistress agent with no side effects. Furthermore, the selected lead was also evaluated for stability by molecular dynamic stimulation as well as for pharmacokinetics and toxicity profile. It has been concluded stable conformation of withanolide-B without presence of any major toxic effects. As a result, the in silico molecular docking technique is a highly successful method for selecting a prospective herbal lead molecule with respect to a specific target, and future research can pave the way for further exploration in the drug development field.

Recent insight into the biological activities and SAR of quinolone derivatives as multifunctional scaffold.

Quinolones are a type of bicyclic privileged building block with immense therapeutic potential. They are known for their crucial role in modulating numerous diseases conditions. In the present review, quinolone and its derivatives with different pharmacological properties like antibacterial, anticancer, anti-HIV, antitubercular and antimalarial activities are described on the basis of their structure activity relationship studies. Literature is mainly focused on the structural changes responsible for the significant increase in the therapeutic profile of the quinolone scaffold and its derivatives. The substitution pattern in the scaffold responsible for a substantial rise in the potency of specific activity has also been discussed, while emphasizing their potential as lead molecule for the drug discovery and development. Moreover, updates of recent research findings on this scaffold are also discussed.