Ligand-based virtual screening, molecular docking, and molecular dynamics of eugenol analogs as potential acetylcholinesterase inhibitors with biological activity against Spodoptera frugiperda

Méndez-Álvarez, Domingo; Herrera-Mayorga, Verónica; Juárez-Saldívar, Alfredo; Paz-González, Alma D.; Ortiz-Pérez, Eyrá; Bandyopadhyay, Debasish; Pérez‐Sánchez, Horacio; Rivera, Gildardo

doi:10.1007/s11030-021-10312-5

Cited by 7 publications

(3 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In general, the compounds P9 , E2 , and the control ligand in complex with Lm TIM had a fluctuating behavior that suggests a change in the initial binding position [ 38 , 39 ]. The complex with the lowest RMSD and minimal differences between oscillations has been described as the most stable [ 40 ]. In this sense, the E2 - Lm TIM complex showed less oscillation and better stability after 20 ns than the P9 - Lm TIM complex.…”

Section: Resultsmentioning

confidence: 99%

Virtual Screening of Benzimidazole Derivatives as Potential Triose Phosphate Isomerase Inhibitors with Biological Activity against Leishmania mexicana

et al. 2023

Self Cite

View full text Add to dashboard Cite

Leishmania mexicana (L. mexicana) is a causal agent of cutaneous leishmaniasis (CL), a “Neglected disease”, for which the search for new drugs is a priority. Benzimidazole is a scaffold used to develop antiparasitic drugs; therefore, it is interesting molecule against L. mexicana. In this work, a ligand-based virtual screening (LBVS) of the ZINC15 database was performed. Subsequently, molecular docking was used to predict the compounds with potential binding at the dimer interface of triosephosphate isomerase (TIM) of L. mexicana (LmTIM). Compounds were selected on binding patterns, cost, and commercial availability for in vitro assays against L. mexicana blood promastigotes. The compounds were analyzed by molecular dynamics simulation on LmTIM and its homologous human TIM. Finally, the physicochemical and pharmacokinetic properties were determined in silico. A total of 175 molecules with docking scores between −10.8 and −9.0 Kcal/mol were obtained. Compound E2 showed the best leishmanicidal activity (IC50 = 4.04 µM) with a value similar to the reference drug pentamidine (IC50 = 2.23 µM). Molecular dynamics analysis predicted low affinity for human TIM. Furthermore, the pharmacokinetic and toxicological properties of the compounds were suitable for developing new leishmanicidal agents.

show abstract

Section: Resultsmentioning

confidence: 99%

Virtual Screening of Benzimidazole Derivatives as Potential Triose Phosphate Isomerase Inhibitors with Biological Activity against Leishmania mexicana

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…The apo- Lm TIM-free protein was also analyzed with these results, being comparable to those previously reported by our work group [ 45 ]. In general, compounds B-3 and S-8 in complex with Lm TIM showed a more stable behavior than the complex with the control ligand ( BTZ – Lm TIM) due to their low RMSD and minimal differences in oscillations since they have been generally described in most molecular dynamics simulations with RMSD values < 2 Å with fluctuations between 0.7 and 9 Å, respectively [ 46 , 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as Leishmania mexicana Inhibitors

et al. 2023

Self Cite

View full text Add to dashboard Cite

Cutaneous leishmaniasis (CL) is a public health problem affecting more than 98 countries worldwide. No vaccine is available to prevent the disease, and available medical treatments cause serious side effects. Additionally, treatment failure and parasite resistance have made the development of new drugs against CL necessary. In this work, a virtual screening of natural products from the BIOFACQUIM and Selleckchem databases was performed using the method of molecular docking at the triosephosphate isomerase (TIM) enzyme interface of Leishmania mexicana (L. mexicana). Finally, the in vitro leishmanicidal activity of selected compounds against two strains of L. mexicana, their cytotoxicity, and selectivity index were determined. The top ten compounds were obtained based on the docking results. Four were selected for further in silico analysis. The ADME-Tox analysis of the selected compounds predicted favorable physicochemical and toxicological properties. Among these four compounds, S-8 (IC50 = 55 µM) demonstrated a two-fold higher activity against the promastigote of both L. mexicana strains than the reference drug glucantime (IC50 = 133 µM). This finding encourages the screening of natural products as new anti-leishmania agents.

show abstract

“…The free protein ( Tc TIM), L1- Tc TIM, B2- Tc TIM, B5- Tc TIM, and BTS- Tc TIM were analyzed by molecular dynamics simulations to determine the stability of the complex formed [ 44 , 45 ]. In addition, the complex of the ligand co-crystallized with the protein (BTS- Tc TIM) was analyzed to expand the information that has been described in the literature.…”

Section: Discussionmentioning

confidence: 99%

Ligand-Based Virtual Screening and Molecular Docking of Benzimidazoles as Potential Inhibitors of Triosephosphate Isomerase Identified New Trypanocidal Agents

Vázquez-Jiménez

Juárez-Saldívar

Gómez-Escobedo

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Trypanosoma cruzi (T. cruzi) is a parasite that affects humans and other mammals. T. cruzi depends on glycolysis as a source of adenosine triphosphate (ATP) supply, and triosephosphate isomerase (TIM) plays a key role in this metabolic pathway. This enzyme is an attractive target for the design of new trypanocidal drugs. In this study, a ligand-based virtual screening (LBVS) from the ZINC15 database using benzimidazole as a scaffold was accomplished. Later, a molecular docking on the interface of T. cruzi TIM (TcTIM) was performed and the compounds were grouped by interaction profiles. Subsequently, a selection of compounds was made based on cost and availability for in vitro evaluation against blood trypomastigotes. Finally, the compounds were analyzed by molecular dynamics simulation, and physicochemical and pharmacokinetic properties were determined using SwissADME software. A total of 1604 molecules were obtained as potential TcTIM inhibitors. BP2 and BP5 showed trypanocidal activity with half-maximal lytic concentration (LC50) values of 155.86 and 226.30 µM, respectively. Molecular docking and molecular dynamics simulation analyzes showed a favorable docking score of BP5 compound on TcTIM. Additionally, BP5 showed a low docking score (−5.9 Kcal/mol) on human TIM compared to the control ligand (−7.2 Kcal/mol). Both compounds BP2 and BP5 showed good physicochemical and pharmacokinetic properties as new anti-T. cruzi agents.

show abstract

Ligand-based virtual screening, molecular docking, and molecular dynamics of eugenol analogs as potential acetylcholinesterase inhibitors with biological activity against Spodoptera frugiperda

Cited by 7 publications

References 41 publications

Virtual Screening of Benzimidazole Derivatives as Potential Triose Phosphate Isomerase Inhibitors with Biological Activity against Leishmania mexicana

Virtual Screening of Benzimidazole Derivatives as Potential Triose Phosphate Isomerase Inhibitors with Biological Activity against Leishmania mexicana

Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as Leishmania mexicana Inhibitors

Ligand-Based Virtual Screening and Molecular Docking of Benzimidazoles as Potential Inhibitors of Triosephosphate Isomerase Identified New Trypanocidal Agents

Contact Info

Product

Resources

About