Exploring antibiofilm potential of some new imidazole analogs against C. albicans: synthesis, antifungal activity, molecular docking and molecular dynamics studies

Abstract

A series of 1, 2, 4, 5-tetrasubstituted imidazole derivatives were synthesized and their antibiofilm potential against Candida albicans was evaluated in vitro. Two of the synthesized derivatives 5e (IC₅₀ = 25 µg/mL) and 5m (IC₅₀ = 6 µg/mL),displayed better antifungal and antibiofilm potential than the standard drug Fluconazole (IC₅₀ = 40 µg/mL) against C. albicans. Based on the in vitro results, we escalated the real time polymerase chain reaction (RT-PCR) analysis to gain knowledge of the enzymes expressed in the generation and maintenance of biofilms and the mechanism of biofilm inhibition by the synthesized analogues. We then investigated the possible interactions of the synthesized compounds in inhibiting agglutinin-like proteins, namely Als3, Als4 and Als6 were prominently down-regulated using in-silico molecular docking analysis against the previously available crystal structure of Als3 and constructed structure of Als4 and Als6 using the SWISS-MODEL server. The stability and energy of the agglutinin-like proteins–ligand complexes were evaluated using molecular dynamics simulations (MDS). According to the 100 ns MDS, all the compounds remained stable, formed a maximum of 3, and on average 2 hydrogen bonds, and Gibb’s free energy landscape analysis suggested greater affinity of the compounds 5e and 5m toward Als4 protein.

Communicated by Ramaswamy H. Sarma

Keywords:

• Imidazole
• biofilm activity
• molecular docking
• RT-PCR analysis
• molecular dynamics

Acknowledgments

The author SAA extends their sincere appreciation to Researchers Supporting Project number (RSPD2024R744), King Saud University, Riyadh, Saudi Arabia. The authors also thank Principal, Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431 001 (M.S.), India, for providing the laboratory facility.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author SAA extends their sincere appreciation to Researchers Supporting Project number (RSPD2024R744), King Saud University, Riyadh, Saudi Arabia. The authors also thank Principal, Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431 001 (M.S.), India, for providing the laboratory facility.