Synthesis, ADME, Molecular Docking and Biological Evaluation of New 2-Aminobenzothiazloes

Abstract

Background: In recent years, 2-aminobenzothiazoles were reported as antibacterial, antihelmintic, antitumor, antimalarial, antiviral, analgesic and anti-inflammatory agents. Objectives: The study aimed to explore new potential 2-aminobenzothiazoles as antibacterial and anthelmintic agents. Methods: A favorable two-step method was used for the synthesis of new 2-aminobenzothiazole derivatives (4a-4j) by Schiff base. All synthesized compounds were tested for antibacterial activity using an in vitro cup-plate method and antihelmintic activity by recording in vitro earthworm paralysis and death time. Pharmacokinetics in silico studies were performed to predict the drug performance in the body using the Molinspiration kit. The molecular docking was performed to check the catalytic binding site between the dihydrofolate reductase and synthesized compounds (4a-4j). Results: The compound 4d emerged as the most effective vermifuge and vermicide among all tested compounds. The compounds 4c, 4f, 4g, 4i and 4j were examined as highly potent against grampositive bacteria. The compounds 4b, 4h, and 4i showed maximum inhibition against gramnegative bacteria. In support of antibacterial activity, the compounds 4c and 4j showed good binding orientation in the catalytic binding pocket of the DHFR receptor (PDB ID: 4LAE). These synthesized compounds could have evolved to shape orally active compounds shown in pharmacokinetics in silico studies. Conclusions: The research outcomes showed that explored 2-aminobenzothiazoles have good antibacterial and anthelmintic activity.