A review on environmental occurrence, toxicity and microbial degradation of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).

In recent years, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have surfaced as a novel class of pollutants due to their incomplete degradation in wastewater treatment plants and their inherent ability to promote physiological predicaments in humans even at low doses. The occurrence of the most common NSAIDs (diclofenac, ibuprofen, naproxen, and ketoprofen) in river water, groundwater, finished water samples, WWTPs, and hospital wastewater effluents along with their toxicity effects were reviewed. The typical concentrations of NSAIDs in natural waters were mostly below 1 µg/L, the rivers receiving untreated wastewater discharge have often showed higher concentrations, highlighting the importance of effective wastewater treatment. The critical analysis of potential, pathways and mechanisms of microbial degradation of NSAIDs were also done. Although studies on algal and fungal strains were limited, several bacterial strains were known to degrade NSAIDs. This microbial ability is attributed to hydroxylation by cytochrome P450 because of the decrease in drug concentrations in fungal cultures of Phanerochaete sordida YK-624 on incubation with 1-aminobenzotriazole. Moreover, processes like decarboxylation, dehydrogenation, dechlorination, subsequent oxidation, demethylation, etc. also constitute the degradation pathways. A wide array of enzymes like dehydrogenase, oxidoreductase, dioxygenase, monooxygenase, decarboxylase, and many more are upregulated during the degradation process, which indicates the possibility of their involvement in microbial degradation. Specific hindrances in upscaling the process along with analytical research needs were also identified, and novel investigative approaches for future monitoring studies are proposed.

A QSAR model of Olanzapine derivatives as potential inhibitors for 5-HT2A Receptor.

Schizophrenia is a complex, chronic mental disorder, affecting about 21 million people worldwide. It is characterized by symptoms, including distortions in thinking, perception, emotions, disorganized speech, sense of self and behavior. Recently, a numbers of marketed drugs for Schizophrenia are available against dopamine D2 and serotonin 5-HT2A receptors. Here, we docked Olanzapine derivatives (collected from literature) with 5-HT2A Receptor using the program AutoDock 4.2. The docked protein inhibitor complex structure was optimized using molecular dynamics simulation for 5ps with the CHARMM-22 force field using NAMD (NAnoscale Molecular Dynamics program) incorporated in visual molecular dynamics (VMD 1.9.2) and then evaluating the stability of complex structure by calculating RMSD values. NAMD is a parallel, object-oriented molecular dynamics code designed for high-performance simulation of large biomolecular systems. A quantitative structure activity relationship (QSAR) model was built using energy-based descriptors as independent variable and pKi value as dependent variable of eleven known Olanzapine derivatives with 5-HT2A Receptor, yielding correlation coefficient r2 of 0.63861. The predictive performance of QSAR model was assessed using different crossvalidation procedures. Our results suggest that a ligand-receptor binding interaction for 5-HT2A receptor using a QSAR model is promising approach to design more potent 5-HT2A receptor inhibitors prior to their synthesis.