Identification of potent natural compounds in targeting Leishmania major CYP51 and GP63 proteins using a high-throughput computationally enhanced screening

Abstract

Background Leishmaniasis is a disease caused by protozoan forms called Leishmania which infect animals and humans. The drugs have been in use since half a century due to which there have been mutations in the microbe-facilitating drug resistance. So this provides a reason for searching for effective drugs for the disease. In the current work, an effort has been to find such drugs that act on disease-relevant receptors by similarity indexing method, molecular docking, and dynamics studies. The study focused on the rapid expansion of potential anti-leishmanial compounds that could function as novel natural compound structures for future drug Results Similarity indexing of existing drugs with natural compounds using Tanimoto clustering resulted in 4 compounds with similarity index of greater than 0.7 (70% similarity). The molecular docking of the resulted compounds was carried out with therapeutic targets CYP51 and GP63 proteins. N-methyltyrosyl-N-methyltyrosyl-leucyl-alanine from Streptomyces griseus showed higher binding affinity in comparison to inhibitor and other selected natural compounds. Simulation studies revealed that the binding configuration of the compound with targets was highly stable all through 10 ns of simulation time with intact hydrogen bonding. Conclusions The molecular docking and molecular dynamics studies for the selected natural bioactive compound N-methyltyrosyl-N-methyltyrosyl-leucyl-alanine from Streptomyces griseus showed better binding affinity with the selected therapeutics targets and can be further considered for in vitro and in vivo studies which may lead to a possible new drug for the treatment of Leishmaniasis.

Synthesis, Structural Characterizations, and Quantum Chemical Investigations on 1-(3-Methoxy-phenyl)-3-naphthalen-1-yl-propenone

“…The best conformation of the protein–ligand complex was chosen based on binding energy and hydrogen bond interactions. , …”

Investigation of the Fluorescence Turn-off Mechanism, Genome, Molecular Docking In Silico and In Vitro Studies of 2-Acetyl-3H-benzo[f]chromen-3-one

“… 29 The grid box was generated with the specification of 3.5 Ao areas around the bound cocrystallized ligand. 30 …”

“…The crystal structure of the protein was downloaded from the PDB database and a reference-based docking study was carried out using Autodock vinatool . The grid box was generated with the specification of 3.5 Ao areas around the bound cocrystallized ligand …”

“…The In vitro antibacterial capability of the synthesized compound, 2-acetyl-3 H -benzo­[ f ]­chromen-3-one, was evaluated by the agar well diffusion technique according to the method published previously by Yaraguppi et al The pathogens were obtained from the Microbial Type Culture Collection and Gene Bank (MTCC), Chandigarh, and the National Collection of Industrial Microorganisms (NCIM), Pune. The antibacterial effect was assessed against Gram-positive bacteria like Micrococcus luteus (NCIM 2871), Bacillus cereus (NCIM 2217), Bacillus subtilis (NCIM 2718), and Staphylococcus aureus (MTCC 737).…”

“…29 The grid box was generated with the specification of 3.5 Ao areas around the bound cocrystallized ligand. 30 2.5. Antimicrobial Activity of 2-Acetyl-3H-benzo[f ]chromen-3-one.…”