Novel Galactopyranoside Esters: Synthesis, Mechanism, In Vitro Antimicrobial Evaluation and Molecular Docking Studies

Abstract

One-step direct unimolar valeroylation of methyl α-D-galactopyranoside (MDG) mainly furnished the corresponding 6-O-valeroate. However, DMAP catalyzed a similar reaction that produced 2,6-di-O-valeroate and 6-O-valeroate, with the reactivity sequence as 6-OH > 2-OH > 3-OH,4-OH. To obtain novel antimicrobial agents, 6-O- and 2,6-di-O-valeroate were converted into several 2,3,4-tri-O- and 3,4-di-O-acyl esters, respectively, with other acylating agents in good yields. The PASS activity spectra along with in vitro antimicrobial evaluation clearly indicated that these MDG esters had better antifungal activities than antibacterial agents. To rationalize higher antifungal potentiality, molecular docking was conducted with sterol 14α-demethylase (PDB ID: 4UYL, Aspergillus fumigatus), which clearly supported the in vitro antifungal results. In particular, MDG ester 7–12 showed higher binding energy than the antifungal drug, fluconazole. Additionally, these compounds were found to have more promising binding energy with the SARS-CoV-2 main protease (6LU7) than tetracycline, fluconazole, and native inhibitor N3. Detailed investigation of Ki values, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and the drug-likeness profile indicated that most of these compounds satisfy the drug-likeness evaluation, bioavailability, and safety tests, and hence, these synthetic novel MDG esters could be new antifungal and antiviral drugs.

Phytochemical Constituents and In-Vitro Anticancer Activity of some Medicinal Plant Extracts against MCF-7 and MDA-MB-435 Human Breast Cancer Cell L

“…Galactopyranoside methyl alpha (21.92%) in flaxseed and its analogs was reported as a potential antimicrobial and antiviral inhibitor of protease enzyme and as antimicrobial and anticancer. 59 GC-MS profile of garlic (A. sativum) ethanol extract is characterized by the presence of di-n-octyl phthalate as a major compound in addition to phytosterol, fatty acid, and vitamin E. Similar bioactive compounds in garlic extract were analyzed previously using HPLC/QQQ/MS. 60 Although fresh garlic is characterized by the presence of sulfur compounds in higher concentrations but GC-MS analysis of ethanol extract showed a lower percentage of sulfur -containing compounds this may be attributed to the different extraction techniques.…”

Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition

“…Amino acid residues with missing atoms and those with alternate positions for some of their atoms were optimized. All synthesized derivatives were chemically and energetically optimized according to Nafie et al, 2019 [ 45 , 46 ]. The grid-box size (center_x_y_z: –24.11, −13.01, and 3.64; spacing dimensions of the grid were of 1 Å) was prepared, AutoDock Vina was used for molecular docking for binding poses generation and docking score calculations [ 47 ], and Finally, the docked chemical and protein interaction with the key amino acids was analysed using Chimera, a visualisation software.…”

Rhamnopyranoside Pivaloyl Esters as Black and White Fungus Inhibitors: Molecular Docking, Dynamics and ADMET Analysis

“…The molecular docking studies were conducted to assess the binding interactions and the ligands' binding orientations with regard to the protein binding site with four targeted proteins, including black and white fungus. Molecular docking has been performed to determine how much binding energy forms during the formation of a drug-protein complex, and affinities of -6.00 kcal/mol have been considered standard affinities [38]. According to the findings of the research (Table 4), 9 had the greatest interaction affinity or binding affinity among all the investigated compounds against black fungus proteins, which are -8.2 kcal/mol for Mycolicibacterium smegmatis (7D6X) and -8.7 kcal/mol for Rhizomucor miehei (4WTP).…”