New anti-candida active nitrogen-containing bisphosphonates as inhibitors of farnesyl pyrophosphate synthase Candida albicans

• Published in: Ukrainian biochemical journal Vol. 91; no. 3; pp. 78 - 89
• Main Authors: Metelytsia, L. O., Hodyna, D. M., Kobzar, O. L., Kovalishyn, V. V., Semenyuta, I. V.
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry 01.05.2019
• Subjects: Candida albicans; farnesyl pyrophosphate synthase; homology modeling; molecular docking; nitrogen-containing bisphosphonates
• ISSN: 2409-4943; 2413-5003
• DOI: 10.15407/ubj91.03.078

In our previous work, a number of new nitrogen-containing bisphosphonates (N-BPs) with high predicted and experimental antifungal activity were presented as potential Candida albicans farnesyl pyrophos­phate synthase (FPPS) inhibitors. To confirm this hypothesis, a homologous C. albicans FPPS model with high-quality scores has been developed and used in present work to study the molecular mechanism of nit­rogen-containing bisphosphonates action as anti-Candida agents. The known FPPS inhibitors ammonium 2-(Pyridin-2-ylamino)ethylidene-1,1-bisphosphonate, risedronate and alendronate were used in molecular docking analysis. The molecular docking analysis of the new N-BPs demonstrated a number of common features of all ligand’s interaction in the active center of FPPS C. albicans. It is established that the ligands phosphonate groups are the key elements in the formation of the stable ligand-protein complexes with binding energy in a range (ΔG) from –6.6 to –7.1 kcal/mol due to a significant number of electrostatic, hydrogen and metal-acceptor bonds. It is confirmed that the new studied N-BPs 1 and 3 with high anti-Candida activity are FPPS inhibitors.