PMID- 37878040
OWN - NLM
STAT- Publisher
LR  - 20231025
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
DP  - 2023 Oct 25
TI  - Synthesis, structural and X-ray analysis evaluations and computational studies of 
      newly tetrahydroisoquinoline derivatives as potent against microsomal 
      prostaglandin E synthase 1.
PG  - 1-15
LID - 10.1080/07391102.2023.2272745 [doi]
AB  - Tetrahydroisoquinolines (THIQs) are a significant class within the broad range of 
      natural compounds known as isoquinoline alkaloids. Natural and manmade drugs 
      based on THIQ have a variety of biological effects that protect against different 
      infectious pathogens and neurological diseases. In this study, two new THIQ 
      derivatives were synthesized and characterized using by X-ray crystallographic 
      analysis. The performed Hirshfeld analysis shows the intermolecular interactions 
      and reactive sites of compounds. The 2D fingerprints reveal dominants H...C 
      interactions up to 8.8% in 3a while 43% H...H elemental interactions are observed 
      in compound 3b. In studied compound 3a, the repulsion energies (k(-rep)) dominate 
      the other energies where the highest amount of 63.8 kJ/mol is obtained whereas 3b 
      has a significant contribution from E(-dis) to the total energy of the molecule 
      from the energy framework study. Moreover, the density functional theory study 
      reveals better thermodynamic and electronic stabilities. These compounds have 
      reduced HOMO-LUMO gaps (E(H-L)) ranging from 3.66 to 3.60 eV, indicating their 
      remarkable conductive and electronic properties. The significant reduction in 
      E(H-L) also guarantees our synthesized compounds' soft nature and reactivity. Our 
      studied compound's NBO charges and MEPs analysis show electron-rich sites and 
      donor-acceptor mechanism. Our synthesized compounds have remarkable 
      polarizability (alpha(o)) and hyperpolarizability (beta(o)) values 
      (446.23 - 1312.73 au), which indicates their optical and nonlinear optical 
      properties. The density of states spectra further illustrates their notable 
      structural-electronic properties and reduced band gaps. Based on structural 
      activity relationship studies, we found that these tetrahydro-isoquinolines 
      derivatives are potent against microsomal prostaglandin E synthase 1(MPGES1), the 
      docking analysis shows that studied compounds have a good binding affinity with 
      MPGES1, and further ADME/T analysis was carried out for both compounds. In 
      addtion to this molecular dynamics, studies were performed to understand the 
      binding stability of both compounds in protien complex system during 100 ns 
      simulation.Communicated by Ramaswamy H. Sarma.
FAU - Mohamed, Shaaban K
AU  - Mohamed SK
AD  - Chemistry and Environmental Division, Manchester Metropolitan University, 
      Manchester, England.
FAU - Karthikeyan, Subramani
AU  - Karthikeyan S
AD  - Center for Healthcare Advancement, Innovation and Research, Vellore Institute of 
      Technology University, Chennai Campus, Chennai, India.
FAU - Khamies, Esraa
AU  - Khamies E
AD  - Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt.
FAU - Ahsin, Atazaz
AU  - Ahsin A
AD  - Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, 
      Chinese Academy of Sciences, Beijing, China.
AD  - School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, 
      China.
FAU - Bakhite, Etify
AU  - Bakhite E
AD  - Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt.
FAU - S Marae, Islam
AU  - S Marae I
AD  - Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt.
FAU - I El-Emary, Talaat
AU  - I El-Emary T
AD  - Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt.
FAU - Mague, Joel T
AU  - Mague JT
AD  - Department of Chemistry, Tulane University, New Orleans, LA, USA.
FAU - I Said, Awad
AU  - I Said A
AD  - Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt.
FAU - Al-Salahi, Rashad
AU  - Al-Salahi R
AD  - Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud 
      University, Riyadh, Saudi Arabia.
FAU - El Bakri, Youness
AU  - El Bakri Y
AUID- ORCID: 0000-0002-5759-6568
AD  - Department of Theoretical and Applied Chemistry, South Ural State University, 
      Chelyabinsk, Russian Federation.
LA  - eng
PT  - Journal Article
DEP - 20231025
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
SB  - IM
OTO - NOTNLM
OT  - ADMET
OT  - DFT calculation
OT  - Tetrahydroisoquinoline
OT  - crystal structure
OT  - molecular docking
OT  - nonlinear optical properties
EDAT- 2023/10/25 12:42
MHDA- 2023/10/25 12:42
CRDT- 2023/10/25 11:04
PHST- 2023/10/25 12:42 [medline]
PHST- 2023/10/25 12:42 [pubmed]
PHST- 2023/10/25 11:04 [entrez]
AID - 10.1080/07391102.2023.2272745 [doi]
PST - aheadofprint
SO  - J Biomol Struct Dyn. 2023 Oct 25:1-15. doi: 10.1080/07391102.2023.2272745.