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In the present work, OECD guidelines have been followed for developing QSAR (Quantitative Structure-Activity Relationship) models for anti-HAT (Human African trypanosomiasis) activity of two hundred and seventy pyrazole sulphonamides. The newly developed easily interpretable multiple QSAR models have been successful in identification of many privileged as well as under-privileged molecular descriptors, which could be highly useful for future use of these models by expert and non-experts of QSAR. The multiple QSAR models satisfy threshold values for many statistical parameters such as R2 = 0.80–0.83, Q2 = 0.79–0.81, CCCext = 0.82–0.84, etc. thereby assuring good external predictive ability of the models. The multiple QSAR and pharmacophoric models successfully identified that N,4-disubstituted-benzenesulfonamide moiety, frequency of occurrence of H-bond acceptor from Oxygen atom within nine bonds and some other pharmacophoric features that govern the anti-HAT activity of pyrazole sulphonamides. The results could be very useful to synthetic/medicinal chemists for future modifications of pyrazole sulphonamides as drug candidates.

Multiple discrete quantitative structure–activity relationships (QSARs) models were constructed for the anticancer activity of α, β-unsaturated carbonyl-based compounds, oxime and oxime ether analogues with a variety of substituents like Br, OH, –OMe, etc. at different positions. A big pool of descriptors was considered for QSAR model building. Genetic algorithm (GA), available in QSARINS-Chem, was executed to choose optimum number and set of descriptors to create the multi-linear regression equations for a dataset of sixty-nine compounds. The newly developed five parametric models were subjected to exhaustive internal and external validation along with Y-scrambling using QSARINS-Chem, according to the OECD principles for QSAR model validation. The models were built using easily interpretable descriptors and accepted after confirming statistically robustness with high external predictive ability. The five parametric models were found to have R2 = 0.80 to 0.86, R2ex = 0.75 to 0.84, and CCCex = 0.85 to 0.90. The models indicate that frequency of nitrogen and oxygen atoms separated by five bonds from each other and internal electronic environment of the molecule have correlation with the anticancer activity.

Synthesis of some new pyrazole, pyridazine, pyridine, chalcone, hydrazone derivatives containing thiophene ring has been carried out by simple, efficient and good yielding routes starting from the versatile and readily accessible ethyl 5-acetyl-4-phenyl- 2-(phenylamino)thiophene-3-carboxylate (1). The structure of the products has been elucidated from their spectral and elemental analyses. X-ray crystallography of compound 1 confirmed its structure.

In the present work, sixty substituted 2-Phenylimidazopyridines previously reported with potent anti-human African trypanosomiasis (HAT) activity were selected to build genetic algorithm (GA) based QSAR models to determine the structural features that have significant correlation with the activity. Multiple QSAR models were built using easily interpretable descriptors that are directly associated with the presence or the absence of a structural scaffold, or a specific atom. All the QSAR models have been thoroughly validated according to the OECD principles. All the QSAR models are statistically very robust (R2 = 0.80–0.87) with high external predictive ability (CCCex = 0.81–0.92). The QSAR analysis reveals that the HAT activity has good correlation with the presence of five membered rings in the molecule.

Fine particulate matter (PM 2.5) is the principal instigators of adverse health events, yet gaps still remain in understanding the mechanism mediating its toxic response. Similar to nanoparticles, PM 2.5, with large surface area to volume ratio, can absorb multipollutants in air, displaying toxicity profiles that are very different from those of coarse particles of the same composition. One particularly relevant interaction is that of PM 2.5 and the anthropogenic metals. In this study, we used carbon black nanoparticle (CBs) and metal ions as model materials to investigate the synergistic pulmonary toxicity and its mechanism. We demonstrated that excessive metal contaminants adsorbed on CBs contributed to the observed toxic effects both in vitro and in C57BL6 mice intratracheal instillation model. Significantly, we found that autophagy and lysosomal dysfunction accounted for the synergistic pulmonary toxic effect of co-exposure to CBs and metals. Our findings provide a new insight into understanding the toxicological and healthy effects of fine particles, which have potential to aid in mitigating their adverse health effect.

ABBV-075 (Mivebresib) analogues were reported to have BET family bromodomain binding affinity Ki in nano-molar (nM) range (0.8 to 3000 nM). But future optimizations are required to achieve a drug-like molecule with retention of high binding affinity and optimum ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) profile. This could be achieved by identifying the pharmacophoric features (salient and concealed) using modern techniques like CADD (Computer-Aided Drug Designing). Therefore, in the present work, QSAR (Quantitative structure-activity relationship) analysis, a thriving CADD branch, has been executed to achieve the determined objectives. The developed QSAR model is statistically acceptable with robust fitting, high internal and external predictive ability. The developed model fulfils the threshold values for a good number of statistical parameters like R2 = 0.80, R2CV = 0.77, etc. The analysis reveals that non-ring Carbon/Nitrogen atoms, frequency of occurrence of specific combinations of Carbon/Nitrogen atoms with acceptor/donor atoms are important pharmacophoric features for BET binding affinity. Thus, the developed QSAR has a balance of quantitative and qualitative approaches. The results could be useful for future optimizations of Mivebresib analogues .

On-site detection of biomarkers in biofluids found at the crime scene is critically important forensic analysis. However, it remains difficult due to the lack of portable, fast and cheap on-site analytical devices. Traditional methods including polymerase chain reaction (PCR) and electrophoresis requires complicated instrumentation and critical environment. Optical analytical methods can be affected by intrinsic adsorption of complicated sample such as serum. In response, we developed a smartphone-interfaced electrochemical chip device for on-site gender verification. The detection is based on the known difference of biomarkers (creatine kinase (CK) and alanine transaminase (ALT)) between male and female groups. Enzyme cascade reaction converted the enzyme level in biofluids to the consumption of NADH, which can be electrochemically detected by our designed electrochemical chip. Our device retained the capability of gender verification when used in serum and serum stains. The detection can be completed in 20 min. Gender verification of real samples (39 serum samples) demonstrated excellent sensitivity and specificity of this smartphone based device.

Multiple separate quantitative structure–activity relationships (QSARs) models were built for the antiproliferative activity of substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)-benzenesulfonates (PIB-SOs). A variety of descriptors were considered for PIB-SOs through QSAR model building. Genetic algorithm (GA), available in QSARINS, was employed to select optimum number and set of descriptors to build the multi-linear regression equations for a dataset of PIB-SOs. The best three parametric models were subjected to thorough internal and external validation along with Y -randomization using QSARINS, according to the OECD principles for QSAR model validation. The models were found to be statistically robust with high external predictivity. The best three parametric model, based on steric, 3D- and finger print descriptors, was found to have R 2 = 0.91, R 2 ex = 0.89, and CCC ex = 0.94. The CoMFA model, which is based on a combination of steric and electrostatic effects and graphically inferred using contour plots, gave F = 229.34, R 2 CV = 0.71 and R 2 = 0.94. Steric repulsion, frequency of occurrence of carbon and nitrogen at topological distance of seven, and internal electronic environment of the molecule were found to have correlation with the anti-tumor activity of PIB-SOs.