PMID- 33359132
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20210621
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 158
DP  - 2021 Mar 1
TI  - 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.
PG  - 105686
LID - S0928-0987(20)30474-7 [pii]
LID - 10.1016/j.ejps.2020.105686 [doi]
AB  - 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 x 10(4) - 
      4.5 x 10(3) 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.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Wani, Tanveer A
AU  - Wani TA
AD  - Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud 
      University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: 
      twani@ksu.edu.sa.
FAU - Alsaif, Nawaf
AU  - Alsaif N
AD  - Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud 
      University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
FAU - Alanazi, Mohammed M
AU  - Alanazi MM
AD  - Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud 
      University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
FAU - Bakheit, Ahmed H
AU  - Bakheit AH
AD  - Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud 
      University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
FAU - Zargar, Seema
AU  - Zargar S
AD  - Department of Biochemistry, College of Science, King Saud University, PO Box 
      22452, Riyadh 11451, Saudi Arabia.
FAU - Bhat, Mashooq A
AU  - Bhat MA
AD  - Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud 
      University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
LA  - eng
PT  - Journal Article
DEP - 20201226
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
SB  - IM
MH  - Binding Sites
MH  - Circular Dichroism
MH  - Humans
MH  - *Metabolome
MH  - Molecular Docking Simulation
MH  - *Molecular Dynamics Simulation
MH  - Protein Binding
MH  - Spectrometry, Fluorescence
MH  - Thermodynamics
OTO - NOTNLM
OT  - Binding interaction
OT  - Dihydropyrimidine derivative
OT  - Docking
OT  - Fluorescence quenching
OT  - HSA
EDAT- 2020/12/29 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/12/28 10:44
PHST- 2020/10/13 00:00 [received]
PHST- 2020/12/16 00:00 [revised]
PHST- 2020/12/16 00:00 [accepted]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/12/28 10:44 [entrez]
AID - S0928-0987(20)30474-7 [pii]
AID - 10.1016/j.ejps.2020.105686 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2021 Mar 1;158:105686. doi: 10.1016/j.ejps.2020.105686. Epub 
      2020 Dec 26.