Design, synthesis, and in silico studies of benzimidazoles of thymol as potent antiplasmodial and antimicrobial agents

[Display omitted] •Design and synthesis of novel benzimidazoles from naturally occurring phenolic monoterpenoid.•In vitro, Anti-plasmodium, Antimicrobial and Antioxidant study with potential results.•Molecular docking with strong binding interactions with PfDHODH enzyme.•In silico ADME properties and toxicity estimation.•Discussion of structure activity relationship. This study presents an efficient one pot two steps synthesis of a new series of naturally occurring phenolic monoterpenoid based (thymol) benzimidazole derivatives (3a-i) by green approach. The structures of all newly synthesized benzimidazoles are confirmed by 1H NMR, 13C NMR, Mass, and FT-IR spectroscopic analyses. The synthesized compounds were examined for their in vitro antimalarial, antioxidant and antimicrobial activities. Antimalarial activity tested against P. falciparum strain, the IC50 values of all the tested compounds are in the range from 0.32 to 1.54 μg/mL. Biological screening revealed that some synthesized benzimidazoles possess very interesting biological activities. Molecular docking simulation against the potent inhibitors Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme indicated that potent compounds 3a, 3f, and 3 g have significant binding energy (-7.9 to −9.7 Kcal/mol). The in silico ADME properties estimated for the synthesized compounds indicated them as very good oral bioavailability drugs.