Synthesis of novel pyrazolone candidates with studying some biological activities and in-silico studies

Abstract

Pyranopyrazole derivatives have a vital role in the class of organic compounds because of their broad spectrum of biological and pharmacological importance. Our current goal is the [3 + 3] cycloaddition of benzoyl isothiocyanate and pyrazolone 1 to undergo oxidation cyclization, producing pyrazoloxadiazine 3. The diol 5 was obtained as a condensation of two equivalents of 1 with thiophene-2-carboxaldehyde in acetic acid above the sodium acetate mixture. When the condensation was carried out in piperidine under fusion, unsaturated ketone 4 was obtained. The pyrazolo pyran derivative 11 resulted from the [3 + 3] cycloaddition of 1 and cinnamic acid, while the Pyrone derivative was prepared by acylation of 12 with two equivalents of acetic anhydride. Phthalic anhydride undergoes arylation using zinc chloride as a catalyst. The cyclic keto acid 23 was synthesized by the action of succinic anhydride on 12 in the acetic medium, while the latter reacted with cinnamic acid, leading to pyrazole derivative 24. All of these reactions were through the Michael reaction mechanism. All the tested compounds showed good antimicrobial activity against pathogenic microorganisms; newly synthesized compounds were also screened for their antioxidant activity. Rational studies were carried out by the ABTs method to allow a broader choice of activities. In addition, similar off-compounds were conducted. Molecular docking studies with the CB-Dock server and MD simulations were created with the default settings of the Solution Builder on the CHARMM-GUI server at 150 nm. A good correlation was obtained between the experimental results and the theoretical bioavailability predictions using POM theory.

Discovery of Novel and Selective Schiff Base Inhibitors as a Key for Drug Synthesis, Molecular Docking, and Pharmacological Evaluation

“…Thomas Sander created the OSIRIS tool, also known as Osiris Property Explorer, to predict several physicochemical characteristics such as molecular weight, clogP, water solubility, and TPSA. Additionally, it can also assess toxicological properties such as mutagenesis effects, tumorigenicity, irritancy, and reproductive toxicity. − …”

“…Additionally, it can also assess toxicological properties such as mutagenesis effects, tumorigenicity, irritancy, and reproductive toxicity. 51 − 53 …”

“…Molinspiration is offered in different areas of computational biology software, which tell us about the manipulation as well as the processing. The provided tools include the conversion of SD files and SMILES like molecule normalization, formation of tautomers, fragmentation of molecules, calculation of various properties necessary for the quantitative structure–activity relationship (QSAR) used for the molecular docking, drug design, and depiction of high-quality molecules and tools for database, which assist in searches for the substrate. , …”