Spatiotemporal variations, sources, pollution status and health risk assessment of dissolved trace elements in a major Arabian Sea draining river: insights from multivariate statistical and machine learning approaches.

River Mahi drains through semi-arid regions (Western India) and is a major Arabian Sea draining river. As the principal surface water source, its water quality is important to the regional population. Therefore, the river water was sampled extensively (n = 64, 16 locations, 4 seasons and 2 years) and analyzed for 11 trace elements (TEs; Sr, V, Cu, Ni, Zn, Cd, Ba, Cr, Mn, Fe, and Co). Machine learning (ML) and multivariate statistical analysis (MVSA) were applied to investigate their possible sources, spatial-temporal-annual variations, evaluate multiple water quality parameters [heavy metal pollution index (HPI), heavy metal evaluation index (HEI)], and health indices [hazard quotient (HQ), and hazard index (THI)] associated with TEs. TE levels were higher than their corresponding world average values in 100% (Sr, V and Zn), 78%(Cu), 41%(Ni), 27%(Cr), 9%(Cd), 8%(Ba), 8%(Co), 6%(Fe), and 0%(Mn), of the samples. Three principal components (PCs) accounted for 74.5% of the TE variance: PC-1 (Fe, Co, Mn and Cu) and PC-2 (Sr and Ba) are contributed from geogenic sources, while PC-3 (Cr, Ni and Zn) are derived from geogenic and anthropogenic sources. HPI, HEI, HQ and THI all indicate that water quality is good for domestic purposes and poses little hazard. ML identified Random forest as the most suitable model for predicting HEI class (accuracy: 92%, recall: 92% and precision: 94%). Even with a limited dataset, the study underscores the potential application of ML to predictive classification modeling.

Computational assessment of Withania somnifera phytomolecules as putative inhibitors of Mycobacterium tuberculosis CTP synthase PyrG.

Genome evolution of Mycobacterium tuberculosis (Mtb) produces new strains resistant to various pre-existing anti-tubercular drugs. Hence, there is an urgent need to explore potent compounds with the most negligible side effects and effective Mtb inhibition. Mtb PyrG (CTP synthase) is a crucial enzyme for the conversion of the uridine triphosphate (UTP) into cytidine triphosphate (CTP) and is essential for the growth of Mtb. Thus, in this study, phytochemicals of Withania somnifera (W. somnifera) were screened to find the potential inhibitors against Mtb PyrG. Molecular docking resulted in the identification of quercetin 3-rutinoside-7-glucoside, rutin, chlorogenic acid and isochlorogenic acid C with a substantial docking score (from -12.6 to -10.8 kcal/mol) contributed by significant intermolecular interactions. Furthermore, 100 ns molecular dynamics simulation, ADME analysis and free binding energy calculations support the stability of docked complexes and drug-likeness for selected compounds, respectively. Collectively, these findings suggest that phytochemicals present in W. somnifera can be considered for further evaluation against Mtb in a series of in vitro and in vivo models.Communicated by Ramaswamy H. Sarma.

4-Aminoquinoline derivatives: Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites.

Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei. The ED50 values were calculated to be 2.062, 2.231, 1.431, 1.623 and 1.18 mg/kg of body weight for each of the compounds 1m, 1o, 2c, 2j and amodiaquine, respectively. Total doses of 500 mg/kg of body weight were well received. The study suggests that these new 4-aminoquinolines should be used for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax.