Synthesis and molecular docking of some new bis-thiadiazoles as anti-hypertensive α-blocking agents

Abstract

Twelve bis-thiadiazole derivatives were synthesized in high yield via the reaction of 2,2′-terephthaloyl bis(N-phenylhydrazine carbothioamide) with a variety of hydrazonoyl chlorides in ethanol containing catalytic amounts of TEA. All the newly synthesized compounds were characterized by physical and chemical tools (FT-IR, ¹H NMR, ¹³C NMR, and Mass spectrometry). Moreover, all the novel synthesized derivatives were screened for their antihypertensive α-blocking efficacy against to assess their pharmaceutical significance. The encouraging promising results obtained from antihypertensive α-blocking activity studies on the newly synthesized derivatives make the synthesis of a new series of these compounds and studying of their pharmaceutical importance an active area for more and more investigations. The molecular docking of the most active derivative 15?b against the human dopamine D3 receptor was performed by the Molecular Operating Environment (MOE 2014. 0901) program.     

Efficient Synthesis of Olmesartan Medoxomil,an Antihypertensive Drug

This document describes a simple and robust process for the synthesis of olmesartan medoxomil. This tailored process allows us to synthesize olmesartan medoxomil on a large scale with 50% overall yield. Also, our process has excellent control of the impurity profile in all the stages.     

Hydrolysate from Mussel Mytilus galloprovincialis Meat: Enzymatic Hydrolysis,Optimization and Bioactive Properties

Mussel production generates losses and waste since their commercialisation must be aligned with target market criteria. Since mussels are rich in proteins, their meat can be explored as a source of bioactive hydrolysates. Thus, the main objective of this study was to establish the optimal production conditions through two Box–Behnken designs to produce, by enzymatic hydrolysis (using subtilisin and corolase), hydrolysates rich in proteins and with bioactive properties. The factorial design allowed for the evaluation of the effects of three factors (hydrolysis temperature, enzyme ratio, and hydrolysis time) on protein/peptides release as well as antioxidant and anti-hypertensive properties of the hydrolysates. The hydrolysates produced using the optimised conditions using the subtilisin protease showed 45.0 ± 0.38% of protein, antioxidant activity via ORAC method of 485.63 ± 60.65 µmol TE/g of hydrolysate, and an IC₅₀ for the inhibition of ACE of 1.0 ± 0.56 mg of protein/mL. The hydrolysates produced using corolase showed 46.35 ± 1.12% of protein, antioxidant activity of 389.48 ± 0.21 µmol TE/g of hydrolysate, and an IC₅₀ for the inhibition of ACE of 3.7 ± 0.33 mg of protein/mL. Mussel meat losses and waste can be used as a source of hydrolysates rich in peptides with relevant bioactive properties, and showing potential for use as ingredients in different industries, such as food and cosmetics, contributing to a circular economy and reducing world waste.     

Application of Thermal Analysis in The Characterization of Anti-hypertensive Drugs

The present work reports studies of the thermal behaviour of some anti-hypertensive drugs. Their purities were determined by DSC and specialized pharmacopeial methods. The activation energy values suggest the following sequence of satability: nifedipine>propanolol hydrochloride>captoril. Analysis of the DSC data indicated that the degrees of purity of nifedipine, captopril and propanolol hydrochloride were similar to those found by pharmacopeial methods BP 93 and USP 23. The simplicity, speed and low operational costs of thermal analysis justify its application in the quality control of pharmaceutical drugs. This revised version was published online in July 2006 with corrections to the Cover Date.