The quantitative structure–activity relationship (QSAR) analyses were carried out for a series of new side chain modified 4-amino-7-chloroquinolines to find out the structural requirements of their antimalarial activities against both chloroquine sensitive (HB3) and resistant (Dd2) Plasmodium falciparum strain. The statistically significant best 2D QSAR models for Dd2, having correlation coefficient (r2)=0.9188 and cross validated squared correlation coefficient (q2)=0.8349 with external predictive ability (pred_r2)=0.7258 and for HB3, having r2=0.9024, q2=0.8089 and pred_r2=0.7463 were developed by multiple linear regression coupled with genetic algorithm (GA–MLR) and stepwise (SW–MLR) forward algorithm, respectively. The results of the present study may be useful on the designing of more potent analogues as antimalarial agents

Alzheimer’s disease (AD) is a chronic neurodegenerative disease. Current therapies of AD are only symptomatic, therefore the need for the development of new therapies to treat Alzheimer’s disease effectively. To achieve this objective quantitative structure–activity relationship (QSAR) studies were carried out as it provides the rationale for the changes in the structure to have more potent Aβ42 inhibitors or anti-Alzheimer’s agents. Quantitative structure–activity relationship (QSAR) studies were carried out on a series of 34 fused 5,6-bicyclic heterocycles to investigate the structural requirements of their inhibitory activity against Aβ42. The statistically significant best 3D-QSAR model having cross-validated squared correlation coefficient q2=0.8457 with external predictive ability of pred_r2=0.7556 was developed by SW-kNN. Developed kNN–MFA model highlighted the importance of shape of the molecules, i.e., hydrophobic and steric descriptors at the grid points H_83 and S_183, S_227 for γ-secretase binding interaction. This model (3D) was found to yield reliable clues for further optimization of fused 5,6-bicyclic heterocycles in the data set. The information rendered by the 3D-QSAR model may lead to a better understanding of the structural requirements of γ-secretase modulators and can also help in the design of novel potent γ-secretase modulators

Quantitative structure–activity relationship (QSAR) studies were carried out on a series of 35 recently synthesised imidazopyridazine derivatives to investigate the structural requirements of their inhibitory activity against malarial kinase, Plasmodium falciparum protein kinase 7 (PfPK7). Partial least square (PLS) methodology coupled with various feature selection methods, viz. stepwise (SW), genetic algorithm (GA) and simulated annealing, was applied to derive QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The statistically significant best 2D-QSAR model having correlation coefficient r ² = 0.9190 and cross-validated squared correlation coefficient q ² = 0.8575 with external predictive ability of pred_r ² = 0.7212 was developed by SW-PLS with the descriptors like StNE-index, T_N_O_2, T_N_O_7, YcompDipole and SaasCE-index. Molecular field analysis was used to construct the best 3D-QSAR model using GA-PLS method, showing good correlative and predictive capabilities in terms of q ² = 0.7494 and pred_r ² = 0.8841. The information rendered by 2D- and 3D-QSAR models may lead to a better understanding of structural requirements of PfPK7 inhibitors and also aid in designing novel potent antimalarial molecules.

Simple, precise, and accurate UV-Spectrophotometric and high-performance thin-layer chromatography (HPTLC) methods for the simultaneous determination of Nitazoxanide and Ofloxacin in pharmaceutical preparations have been developed and validated. The method was developed using aluminum plates pre-coated with silica gel 60 F₂₅₄ HPTLC plates as a stationary phase with toluene:chloroform:carbon tetra chloride:toluene:glacial acetic acid solutions in the proportion of (10:5:3:0.5 v/v/v/v) as mobile phase. Densitometric quantification was performed at 241 nm. Well-resolved bands were obtained with R_F values 0.36, 0.57 and 0.63 for Rosiglitazone maleate, Nitazoxanide, and Ofloxacin, respectively. Rosiglitazone maleate was used as an internal standard. The calibration curves were linear within the concentration range of 5–25 μg/ml for each drug. Two simple spectrophotometric methods have been developed for simultaneous estimation of Nitazoxanide, and Ofloxacin from tablet dosage form. The first method, simultaneous equation method, involves the measurement of absorbances at two wavelengths 221.8 nm (λ_max of Nitazoxanide) and 244.3 nm (λ_max of Ofloxacin), and the second method is First order derivative spectroscopy, wavelengths selected for quantitation were 263.6 nm for Nitazoxanide and 269.2 nm for Ofloxacin. The proposed method gave good validation results and the statistical analysis performed proved that the method is precise, accurate and reproducible, and hence can be employed for routine analysis of Nitazoxanide and Ofloxacin in bulk and commercial formulations.