Druggable targets of protein tyrosine phosphatase Family, viz. PTP1B, SHP2, Cdc25, and LMW-PTP: Current scenario on medicinal Attributes, and SAR insights.

Protein tyrosine phosphatases (PTPs) are the class of dephosphorylation enzymes that catalyze the removal of phosphate groups from tyrosine residues on proteins responsible for various cellular processes. Any disbalance in signal pathways mediated by PTPs leads to various disease conditions like diabetes, obesity, cancers, and autoimmune disorders. Amongst the PTP superfamily, PTP1B, SHP2, Cdc25, and LMW-PTP have been prioritized as druggable targets for developing medicinal agents. PTP1B is an intracellular PTP enzyme that downregulates insulin and leptin signaling pathways and is involved in insulin resistance and glucose homeostasis. SHP2 is involved in the RAS-MAPK pathway and T cell immunity. Cdk-cyclin complex activation occurs by Cdc25-PTPs involved in cell cycle regulation. LMW-PTPs are involved in PDGF/PDGFR, Eph/ephrin, and insulin signaling pathways, resulting in certain diseases like diabetes mellitus, obesity, and cancer. The signaling cascades of PTP1B, SHP2, Cdc25, and LMW-PTPs have been described to rationalize their medicinal importance in the pathophysiology of diabetes, obesity, and cancer. Their binding sites have been explored to overcome the hurdles in discovering target selective molecules with optimum potency. Recent developments in the synthetic molecules bearing heterocyclic moieties against these targets have been explored to gain insight into structural features. The elaborated SAR investigation revealed the effect of substituents on the potency and target selectivity, which can be implicated in the further discovery of newer medicinal agents targeting the druggable members of the PTP superfamily.

Water toxicants: a comprehension on their health concerns, detection, and remediation.

Water is an essential moiety for the human use since a long time. Availability of good-quality water is very essential, as it is used in almost all the industrial, agricultural, and household activities. However, several factors such as increased urbanization and industrialization, extensive use of chemicals, natural weathering of rocks, and human ignorance led to incorporation of enormous toxicants into the water. The water toxicants are broadly classified as inorganic, organic, and radiological toxicants. Inorganic toxicants include heavy metals (As, Cr, Cd, Hg, Ni, Pb) and metalloids, ammonia, nitrate, and fluoride. Uranium is included in radiological toxicants which also causes chemical toxicity. Organic pollutants include polycyclic aromatic hydrocarbons, polychlorinated biphenyls, phenolic compounds, phthalate esters, pesticides, pharmaceutical and personal care products, perchlorates, and flame retardants. These toxicants are harmful for the ecosystem as well as for the human beings causing different types of health complications like lung cancer, nasal cancer, gingivitis, severe vomiting and abdominal pain, hormonal imbalance, skeletal damage, neurotoxicity like Alzheimer and Parkinson disease, renal toxicity, nephrotoxicity, etc. The USEPA and WHO specified the permissible concentration of these pollutants in the drinking water. Determination techniques having high sensitivity, low cost, rapid onsite, and real-time detection of traces of water pollutants are discussed. This review also covers in depth about the remediation techniques, for the control of water toxicants, such as chelation of the heavy metals, intoxication of pollutants using various plants, adsorption of toxicants using different sorbent medias, and photocatalytic breakdown of persistent organic pollutants (POPs).