Details

Autor(en) / Beteiligte

• Wani, Tanveer A.
• Alsaif, Nawaf
• Alanazi, Mohammed M.
• Bakheit, Ahmed H.
• Zargar, Seema
• Bhat, Mashooq A.

Titel

A potential anticancer dihydropyrimidine derivative and its protein binding mechanism by multispectroscopic, molecular docking and molecular dynamic simulation along with its in-silico toxicity and metabolic profile

Ist Teil von

• European journal of pharmaceutical sciences, 2021-03, Vol.158, p.105686-105686, Article 105686

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 1Plasma protein binding has a major role in drug transportation and distribution.2Protein binding influences the pharmacokinetics and pharmacodynamics of drugs.3This study would be highly beneficial in the preclinical development of DHP4The study will provide information mechanism of binding forces and site involved while interacting with serum albumin.5In silico toxicity profile of DHP shows the drug to be safe for preclinical studies Human serum albumin (HSA) is the core protein in the systemic circulation and has a fundamental role in transportation and distribution of ligands in-vivo. In this study, a newly synthesized and patented anticancer dihydropyrimidine derivative; 4-(4-ethoxyphenyl)-5-(3,4,5- trimethoxybenzoyl)-3,4-dihydropyrimidin-2(1H)-one (DHP) was evaluated for its binding to HSA. Ligand-HSA interaction is significant factor to attribute the toxicity or therapeutic potential to a ligand. Multi-spectroscopic studies combined with molecular modelling and molecular dynamic simulation (MDS) were conducted to understand the HSA-DHP binding mechanism. In-silico evaluation of DHP for its toxicity and metabolism was also conducted. Reduction in the binding constants was observed from 6.71 × 104 – 4.5 × 103 at increased temperatures which indicates moderate binding and the interaction was found to follow a static quenching mechanism. Further, Site I on HSA for DHP was established by competition with site specific markers and the results were supported by molecular docking. The stability of the HSA-DHP complex was established with MDS studies. Thermodynamics parameters revealed involvement of hydrogen bonding and van der Waals forces for HSA-DHP binding. An in-silico evaluation of DHP for its toxicity and metabolism provided that the synthesized compound was potentially safe and could be a promising candidate for further studies. [Display omitted]