In silico ADME predictions and in vitro antibacterial evaluation of 2-hydroxy benzothiazole-based 1,3,4-oxadiazole derivatives

Abstract

In the present work, a library of fifteen 2-hydroxy benzothiazole-linked 1,3,4-oxadiazole derivatives have been synthesized and confirmed using different analytical techniques. All of the synthesized compounds have been tested for antibacterial and in silico pharmacokinetic studies for the first time. From the ADME predictions, compound 4 showed the highest in silico absorption percentage (86.77%), while most of the compounds showed more than 70% absorption. All of the compounds comply with the Lipinski rule of 5, suggesting that the compounds possess good drug likeness properties upon administration. Furthermore, all of the compounds follow the Veber rule, indicating good bioavailability and good intestinal absorption. The antibacterial results exhibited excellent to moderate activity. Compounds 5, 9, 12, 14, 15, 16, and 17 were the most active compounds against the tested bacterial strains. Compound 14 showed comparable MIC 6.25 ±0.2 µ g/disc to the standard drug amoxicillin against the tested Gram-positive bacterial strains. Compounds 5, 14, 17 exhibited MIC 12.5 ±0.8 µ g/disc, which was comparable to the standard drug against E. faecalis. It can be concluded that the synthesized compound could be used as a lead molecule in the development of new antibacterial agents with high efficacy.

Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies

“…The pharmacological and pharmacokinetic properties of a compound are important parameters in drug development and discovery as theyreduce the time and cost in the development of a drug [ 23 ]. The molecule must satisfy Lipinski and Veber’s rules to be developed as an effective orally available drug.…”

“…Heterocycles form the basic skeleton for a number of molecules of biological interests [20]. 1,3,4-oxadiazole is an important scaffold as it exhibits remarkable pharmacological activities such as anticancer, antiinflammatory, antimicrobial, antiviral, etc [21][22][23][24]. Furthermore, this moiety shows an antiproliferative effect through EGFR kinase inhibition (Figure 1) [25][26][27][28].…”

Synthesis and Biological Evaluation of 1,2,3-Triazole Tethered Thymol-1,3,4-Oxadiazole Derivatives as Anticancer and Antimicrobial Agents

“…The antimicrobial activity of the final compounds was performed by reported methods [ 39 ].The bacterial strains, E. coli (Gram negative), S. aureus (Gram positive), and fungi, Candida albicans , were used for the study. Luria broth Agar and Sabouraud Dextrose Agar were prepared into a petri dish using 25 mL of autoclaved media; 100 μL of diluted broth of freshly prepared E. coli , S. aureus, and C. albicans were spread on Luria Broth Agar and Sabouraud Agar plates, respectively.…”

Design, synthesis, and molecular docking studies of thiazolidinediones as PPAR‐γ agonists and thymidylate synthase inhibitors

“…The molecule to be an orally available must follow the desired pharmacokinetic properties, besides exhibiting potent pharmacological activities. [ 23 ] The molecule should follow Lipinski's rule of 5, that is, hydrogen bond donors (HBD) should be fewer than 5, hydrogen bond acceptors (HBA) should be lesser than 10, molecular weight should be below 500, and calculated logP should be fewer than 5, for an orally available drug.…”