Design, synthesis, chemical characterization, biological evaluation, and docking study of new 1,3,4-oxadiazole homonucleoside analogs

Abstract

Design, synthesis, chemical characterization, biological evaluation, and docking study of new 1, 3, 4-oxadiazole homonucleoside analogues Herein, we report the synthetic strategies and characterization of some novel 1,3,4oxadiazole homonucleoside analogues that are relevant to potential antitumor and cytotoxic activities. The structure of all compounds is confirmed using various spectroscopic methods such as 1 H-NMR, 13 C-NMR, HRMS, and FTIR. These compounds were evaluated against three human cancer cell lines (MCF-7, SKBR3, and HL60 Cell Line). Preliminary investigations showed that the cytotoxic activity was markedly dependent on the nucleobase. Introduction of 5-Iodouracil 4g and Theobromine 6b proved to be extremely beneficial even they were more potent than the reference drug (DOX). Also, the synthesized compounds were tested for their antiviral activities against the human varicella-zoster virus (VZV). The product 4h was (6-azauracil derivative) more potent to the reference (acyclovir) against the deficient TK-VZV strain by about 2-fold. Finally, molecular docking suggested that the anticancer activities of compounds 6b and 4g mediated by inhibiting dual proteins EGFR/HER2 with low micromolar inhibition constant Ki range. The 1,3,4-oxadiazole homonucleosides showed a strong affinity to binding sites of target proteins by forming H-bond, carbon-hydrogen bond, Pi-anion, Pisulfur, Pi-sigma, alkyl, and Pi-alkyl interactions.

Antimicrobial Activity of 1,3,4-Oxadiazole Derivatives

“…Due to the fact that the VZV TK-strain is resistant to conventional antiviral drugs, the synthesized derivative can serve as a leading structure for further research. Additionally, some of the derivatives showed cytotoxic activity [102].…”

The Fellowship of Privileged Scaffolds—One Structure to Inhibit Them All

“…Recently, El Mansouri et al designed and synthesized a series of 1,3,4-oxadiazolepyrimidines and purines hybrids [93]. One of the compounds (58) showed a great potency of action against thymidine kinase-negative strain (TK-VZV) with EC 50 = 50 µM, which is two times better than the activity of Acyclovir (EC 50 = 103 µM) and comparable with Brivudine (35 µM).…”

Efficient one-pot, three-component procedure to prepare new α-aminophosphonate and phosphonic acid acyclic nucleosides

“…The proteins were prepared separately by removing water andco-crystallized ligands bound with the proteins to make receptor free ofany ligand before docking. Then, Polar hydrogens and Gastieger charges were added using the MGL Tools and proteins saved in PDBQT format [55]. Ligand 14a was created separately using ChemDraw Ultra 12.0,energy minimized in Chem3D, torsional bonds of ligand were set flexible and saved in PDBQT format.…”