QSAR Study of (5-Nitroheteroaryl-1,3,4-Thiadiazole-2-yl) Piperazinyl Derivatives to Predict New Similar Compounds as Antileishmanial Agents

Abstract

To search for newer and potent antileishmanial drugs, a series of 36 compounds of 5-(5-nitroheteroaryl-2-yl)-1,3,4-thiadiazole derivatives were subjected to a quantitative structure-activity relationship (QSAR) analysis for studying, interpreting, and predicting activities and designing new compounds using several statistical tools. The multiple linear regression (MLR), nonlinear regression (RNLM), and artificial neural network (ANN) models were developed using 30 molecules having pIC50 ranging from 3.155 to 5.046. The best generated MLR, RNLM, and ANN models show conventional correlation coefficients R of 0.750, 0.782, and 0.967 as well as their leave-one-out cross-validation correlation coefficients RCV of 0.722, 0.744, and 0.720, respectively. The predictive ability of those models was evaluated by the external validation using a test set of 6 molecules with predicted correlation coefficients Rtest of 0.840, 0.850, and 0.802, respectively. The applicability domains of MLR and MNLR transparent models were investigated using William’s plot to detect outliers and outsides compounds. We expect that this study would be of great help in lead optimization for early drug discovery of new similar compounds.

2D‐QSAR and molecular docking studies of carbamate derivatives to discover novel potent anti‐butyrylcholinesterase agents for Alzheimer's disease treatment

“…Quantum descriptors have been calculated to describe the electronic structure of the studied molecules in order to predict their reactivity toward the external environment, and consequently, these descriptors will provide useful information to explain the studied activity. We adopted DFT theory with (B3LYP/ 6‐31G [p, d]) basis to calculate the quantum descriptors based on some comparative QSAR studies having demonstrated that this theory lead to reliable and accurate results 51–53 . The descriptors values of the studied structures are presented in Table S2.…”

Potential for Aedes aegypti Larval Control and Environmental Friendliness of the Compounds Containing 2-Methyl-3,4-dihydroquinazolin-4-one Heterocycle

“…The analysis results of the electric dipole moment values determined by the B3LYP/6-311++G­(d,p) method were consistent with previous studies on organic compounds with mosquito-repellent activity. , The calculated values of the electric dipole moment, HOMO and LUMO energies, and Mulliken charge on the N atoms and ring, logP: octanol–water partition coefficient are presented in Table S2. The results showed that the electric dipole moment values of compounds 4a – 4i ranged from 1.178 to 8.059 D, with the highest value observed for compound 4i , which contains the para -substituted NO 2 group with the lowest HOMO energy value of −7.026 eV.…”

“…The DFT method was employed to investigate the ground-state geometry of the studied compounds. The B3LYP function and the 6-311++g­(d,p) set of basis functions were used in the optimization process using the G09 software. , The optimized structures were analyzed to determine the compound’s energy, charge properties, and vibrational frequencies. The optimization is successful if the optimized structure contains no imaginary frequencies and meets the convergence criteria of the G09 program.…”

“…The analysis results of the electric dipole moment values determined by the B3LYP/6-311++G(d,p) method were consistent with previous studies on organic compounds with mosquito-repellent activity. 29,30 The calculated values of the electric dipole moment, HOMO and LUMO energies, and Mulliken charge on the N atoms and ring, logP: octanol−water partition coefficient are presented in Table S2.…”

Computational study of quinoline-based thiadiazole compounds as potential antileishmanial inhibitors

“…It has been reported in more than 90 countries in Africa, the Americas, and Asia, and it is considered a severe epidemic in several African countries, namely in North, Central, and East Africa, and the Horn of Africa. 1 The parasite is transferred to the human host by the bites of sandflies of the genera Phlebotomine and Leutzomia. 2 Leishmaniasis has infected around 12 million people, resulting in 0.5 million visceral cases and 1.5–2 million instances of cutaneous illness.…”