Molecular modelling and QSAR analysis of some structurally diverse N-type calcium channel blockers

Abstract

A quantitative structure-activity relationship (QSAR) analysis was performed on a data set of 104 molecules showing N-type calcium channel blocking activity. Several types of descriptors, including electrotopological, structural, thermodynamics and ADMET, were used to derive a quantitative relationship between N-type calcium channel blocking activity and structural properties. The genetic algorithm-based genetic function approximation (GFA) method of variable selection was used to generate the 2D-QSAR model. The model was established on a training set of 83 molecules, and validated by a test set of 21 molecules. The model was developed using five information-rich descriptors--Atype_C_24, Atype_N_68, Rotlbonds, S_sssN, and ADME_Solubility--playing an important role in determining N-type calcium channel blocking activity. For the best QSAR model (model 4), the statistics were r (2) = 0.798; q (2) = 0.769; n = 83 for the training set. This model was further validated using the leave-one-out (LOO) cross-validation approach, Fischer statistics (F), Y-randomisation test, and predictions based on the test data set. The resulting descriptors produced by QSAR model 4 were used to identify physico-chemical features relevant to N-type calcium channel blocking activity.

4-[1-(Substituted aryl/alkyl carbonyl)-benzoimidazol-2-yl]-benzenesulfonic acids: Synthesis, antimicrobial activity, QSAR studies, and antiviral evaluation

“…The appearance of singlet around 2.5 d ppm corresponds to the proton of SO 3 H in the NMR of all the compounds indicated the presence of para sulfonyl phenyl nucleus to the 2nd position of synthesized benzimidazoles (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Further the multiplet corresponds to 6 chloride of methacrylic acid.…”

“…The appearance of C]O stretch in the range of 1630e1600 cm À1 indicated the formation of tertiary amides (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) by the reaction of acid chlorides with the 4-(1H-benzoimidazol-2yl)-benzenesulfonic acid. The primary amino group in compound 1 is depicted by the presence of NH asymmetric stretch at 3481.81 cm À1 .…”

“…Furthermore, the topological parameter, Balaban index (J) followed by the electronic parameter, LUMO and topological parameter, valence second order molecular connectivity index ( 2 c v ) is describing the antimicrobial activity of 4-[1-(substituted aryl/alkyl carbonyl)-benzoimidazol-2-yl]-benzenesulfonic acids (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

Ionic Channels as Targets for Drug Design: A Review on Computational Methods

“…Mohan and coworkers studied a data set of compounds with N-type calcium channel blocking activity [86]. They used several descriptors (structure, ADME/Tox, thermodynamics, electrotopological) to derive a quantitative relationship between blocking activity and structural properties.…”

Harnessing Human N‐type Ca2+ Channel Receptor by Identifying the Atomic Hotspot Regions for Its Structure‐Based Blocker Design

“…Owing to the dramatic increase in the availability of 3D structure of protein targets and rapid advancement in computational techniques, structure‐ or ligand‐based inhibitor design has become an integral strategy for both lead generation and lead optimization 5–12. Recently, we have developed a robust 2D‐quantitative‐structure‐activity relationship (QSAR) model for structurally diverse non‐peptidyl derivatives acting as potent NCC blockers 13…”