Next Article in Journal
The Effects of Two Swimming Learning Programs on Children’s Psychophysiological Profile
Previous Article in Journal
Heart Rate Distribution and Aerobic Fitness Changes During Preseason in Elite Soccer Players
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Extended Abstract

Computational Study of Benzimidazole Derivatives as Potential Antifungal Drugs †

by
Dorian Acevedo
* and
Gian Pietro MIscione
Computational Biorganic Chemistry (COBO), Departamento de Química, Universidad de los Andes, Bogotá 111711, Colombia
*
Author to whom correspondence should be addressed.
Presented at the 2nd Molecules Medicinal Chemistry Symposium (MMCS): Facing Novel Challenges in Drug Discovery, Barcelona, Spain, 15–17 May 2019.
Proceedings 2019, 22(1), 91; https://doi.org/10.3390/proceedings2019022091
Published: 2 September 2019
The infection of fungal diseases has increased in these last years due to the rise in immunodeficient patients, the resistance to current drugs, and the lack of design of new and efficient molecules against those pathogens [1]. On the other hand, benzimidazole derivatives have shown inhibitory activity to Cryptococcus Neoformans fungal with MIC 50 (minimal inhibitory concentration) of 31.2, 15.6, and 7.8 µg/mL for DV, NRE, and ACH type compounds, respectively [2]. In order to find new compounds with benzimidazolic scaffolds by modifying functional chemical groups that can have better antifungal activity, we carried out a computational study using molecular docking, molecular dynamics, and MMGBSA (mechanics generalized born and surface area continuum solvation) to screen the affinity of benzimidazolic ligands with two Mycobacterium Turberculosis enzymes (pdb 1E9X y 3IW2). Those enzymes are involved in the synthesis of ergosterol, which is an important component in the cell membrane wall [3]. The accomplishment of the study presented is a good agreement between the computational model and the experimental results and delivered promising compounds as candidate inhibitors based on benzimidazolic scaffold. Furthermore, other studies have reported that compounds with inhibitory capacity to enzyme 1E9X are also potent inhibitors of mycobacterial growth [4]. For this reason, the new benzimidazole derivatives found in this work can be used as effective drugs against infections caused by fungal and Mycobacterium Turberculosis at the same time. Our proposal is based on the fact that ligands have a tight bind with the pocket of enzyme 3IW2.

References

  1. McLean, K.J.; Lafite, P.; Levy, C.; Cheesman, M.R.; Mast, N.; Pikuleva, I.A.; Leys, D.; Munro, A.W. The structure of Mycobacterium tuberculosis CYP125: Molecularbasis for cholesterol binding in a P450 needed for host infection. J. Biol. Chem. 2009, 284, 35524–35533. [Google Scholar] [CrossRef] [PubMed]
  2. Ergosterol Biosynthesis: a Fungal Pathway for Life on Land? Available online: https://www.ncbi.nlm.nih.gov/pubmed/22946816 (accessed on 16 May 2019).
  3. Pfaller, M.A.; Riley, J.; Koerner, T. Effects of terconazole and other azole antifungal agents on the sterol and carbohydrate composition of Candida albicans. Diagn. Microbiol. Infect. Dis. 1990, 13, 31–35. [Google Scholar] [CrossRef] [PubMed]
  4. Parks, L.W.; Casey, W.M. Physiological Implications of Sterol Biosynthesis in Yeast. Annu. Rev. Microbiol. 1995, 49, 95–116. [Google Scholar] [CrossRef] [PubMed]

Share and Cite

MDPI and ACS Style

Acevedo, D.; MIscione, G.P. Computational Study of Benzimidazole Derivatives as Potential Antifungal Drugs. Proceedings 2019, 22, 91. https://doi.org/10.3390/proceedings2019022091

AMA Style

Acevedo D, MIscione GP. Computational Study of Benzimidazole Derivatives as Potential Antifungal Drugs. Proceedings. 2019; 22(1):91. https://doi.org/10.3390/proceedings2019022091

Chicago/Turabian Style

Acevedo, Dorian, and Gian Pietro MIscione. 2019. "Computational Study of Benzimidazole Derivatives as Potential Antifungal Drugs" Proceedings 22, no. 1: 91. https://doi.org/10.3390/proceedings2019022091

Article Metrics

Back to TopTop