Synthesis, In vivo, and In silico Evaluation of New Pyrazoline- Benzothiazole Conjugates as Orally Administered Antiepileptic Agents.

New 2-(4-benzothiazol-2-yl-phenoxy)-1-(3,5-diphenyl-4,5-dihydro-pyrazol-1-yl)-ethanones (9a-o) have been designed and synthesized. The antiepileptic potential of the synthesized compounds has been tested by following standard animal screening models which include maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) models. The study concluded that compounds 9c, 9d, 9f, 9i, 9n, and 9o possessed good antiepileptic potential when compared with standard drugs like carbamazepine and phenytoin. The results of the rotarod performance test also established them without any neurotoxicity. The motor impairment test yielded that the synthesized compounds are also good antidepressants. In-silico studies have been performed to determine the eligibility of synthesized compounds as orally administered molecules and interactions with the target proteins. The result of in-silico studies reinforced results obtained by in vivo study of the synthesized compounds along with their possible mechanism of antiepileptic action i.e. via inhibiting voltage-gated sodium channels (VGSCs) and gamma-aminobutyric acid-A receptor.

Design, Synthesis, In Vivo, and In Silico Evaluation of Benzothiazoles Bearing a 1,3,4-Oxadiazole Moiety as New Antiepileptic Agents.

In the presented manuscript, a new series of 2-[4-methoxy-3-(5-substituted phenyl-[1,3,4]oxadiazol-2-ylmethoxy)-phenyl]-benzothiazoles (6a-n) have been synthesized and studied in vivo and in silico for their anticonvulsant potential. Maximum electroshocks (MES) and subcutaneous pentylenetetrazol (scPTZ) models have been used for in vivo anticonvulsant activity. Auto Dock 4.2 software was used for in silico studies, and the targeted protein was 5IOV.sThe antidepressant activity of selected compounds (most active) was determined as a reduction in locomotor activity through an actophotometer. In vivo and In silico studies proved that among all the synthesized compounds, 6f, 6h, 6j, and 6l were the most potent with no neurotoxicity as compared to conventional drugs (phenytoin and phenobarbital). The in silico studies also indicated about different binding interactions of synthetic compounds to localize the binding receptors. The most likely mode of action for these drugs, according to the docking analysis of active compounds with various targets, is their binding to the VGCC and NMDA receptors.

Insight into the Synthesis, Biological Activity, and Structure-activity Relationship of Benzothiazole and Benzothiazole-hydrazone Derivatives: A Comprehensive Review.

Heterocyclic compounds constitute the most important part of medicinal as well as organic chemistry. Most of the marketed drugs possess therapeutic activity because of the presence of heterocyclic scaffolds as part of their structure. A slight change in the structure of the heterocyclic moieties may result in a major change in the therapeutic response of the drug candidate. Among all heterocycle compounds, the compounds containing nitrogen and sulfur atoms serve as a unique resource for drug development, such as benzothiazoles. Benzothiazole is a benzofused heterocyclic that is widely reported as a constituent of naturally occurring chemicals and chiefly responsible for their pharmacological potential. It was also reported that the pharmacological activity of BTA may also be influenced by its coupling with aldehydes, ketones, or hydrazines to form respected benzothiazole-hydrazone derivatives. The present comprehensive review consists of various synthesis methods, biological activities, and structure-activity relationships of and targets of benzothiazole and benzothiazole-hydrazone derivatives to provide a wide range of information to medicinal chemists for future research work.

Recent Insights on Synthetic Methods and Pharmacological Potential in Relation with Structure of Benzothiazoles.

Benzothiazole is a bicyclic heterocyclic compound that contains benzene fused with 1, 3- thiazole ring. Several researches established the potential of benzothiazoles as important moiety in various adverse pharmacological conditions. Benzothiazole and its derivatives have been in use and marketed as anti-microbial, anti-inflammatory, anti-diabetic, anti-oxidant, anti-convulsant, antitumor, etc. The variations in pharmacological potentials of benzothiazole and its derivatives have been rational with their chemical structure. Nowadays, hybridization of two or more pharmacophores to synthesize a single molecule with potent pharmacological action is used. This helps to synergize pharmacological properties, make interaction possible with many targets, or minimize the adverse effects associated with them. Several synthetic approaches have been reported for benzothiazole and its derivatives. In this present review article, we focused on recently adopted synthetic approaches for the synthesis of the benzothiazole nucleus and its derivatives. The structure-activity relationship in relation to different pharmacological activities has also been highlighted to provide a good understanding to the researchers for future research on benzothiazoles.

Insights into Interactions of Human Cytochrome P450 17A1: A Review.

Cytochrome P450s are a widespread and vast superfamily of hemeprotein monooxygenases that metabolize physiologically essential chemicals necessary for most species' survival, ranging from protists to plants to humans. They catalyze the synthesis of steroid hormones, cholesterol, bile acids, and arachidonate metabolites and the degradation of endogenous compounds, such as steroids, fatty acids, and other catabolizing compounds as an energy source and detoxifying xenobiotics, such as drugs, procarcinogens, and carcinogens. The human CYP17A1 is one of the cytochrome P450 genes located at the 10q chromosome. The gene expression occurs in the adrenals and gonads, with minor amounts in the brain, placenta, and heart. This P450c17 cytochrome gene is a critical steroidogenesis regulator which performs two distinct activities: 17 alpha-hydroxylase activity (converting pregnenolone to 17- hydroxypregnenolone and progesterone to 17-hydroxyprogesterone; these precursors are further processed to provide glucocorticoids and sex hormones) and 17, 20-lyase activity (which converts 17-hydroxypregnenolone to DHEA). Dozens of mutations within CYP17A1 are found to cause 17-alpha-hydroxylase and 17, 20-lyase deficiency. This condition affects the function of certain hormone-producing glands, resulting in high blood pressure levels (hypertension), abnormal sexual development, and other deficiency diseases. This review highlights the changes in CYP17A1 associated with gene-gene interaction, drug-gene interaction, chemical-gene interaction, and its biochemical reactions; they have some insights to correlate with the fascinating functional characteristics of this human steroidogenic gene. The findings of our theoretical results will be helpful to further the design of specific inhibitors of CYP17A1.