PMID- 30195234
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20190128
IS  - 1476-928X (Electronic)
IS  - 1476-9271 (Linking)
VI  - 77
DP  - 2018 Dec
TI  - Computer-aided identification of natural lead compounds as cyclooxygenase-2 
      inhibitors using virtual screening and molecular dynamic simulation.
PG  - 1-16
LID - S1476-9271(18)30157-9 [pii]
LID - 10.1016/j.compbiolchem.2018.07.005 [doi]
AB  - In order to find more natural lead-compounds as inhibitors for Cyclooxygenase-2, 
      the essential structural features for human cyclooxygenase-2 inhibitors and 
      3D-Quantitative structure activity relationship (3D-QSAR) model were carried out 
      based on dataset from three confirmatory bioassays using Phase program. Six point 
      pharmacophore (AAHRRR) of COX-2 selective inhibitors was generated from training 
      set of 52 compounds. The 3D-QSAR model was selected as having favourable 
      statistic measures (R(2) = 0.93, Q(2)(ext) = 0.81) for the training set and test 
      set respectively. This model was developed using the best pharmacophore 
      hypothesis that helped to reveal the essential features responsible for the 
      anti-inflammatory activity. As a result, this pharmacophore hypothesis has aided 
      in the identification of new four natural lead compounds from UNPD database 
      (UNPD100208, UNPD168234, UNPD91145, UNPD57376) that can be used as potential 
      anti-inflammatory agents or as a core structure to develop other more selective 
      molecules. This result was confirmed by molecular docking, which showed that 
      these four natural lead-compounds adopt the same orientation as Rofecoxib in the 
      COX-2 active site. On the other hand, a molecular dynamic simulation (MDS) was 
      applied and repeated on the top ranking complex 5KIR-UNPD100208 and compared with 
      the results of MDS of 5KIR-Rofecoxib. The results from MDS revealed a good 
      stability of the compound UNPD100208 in the active site based on several 
      parameters such as RMSD, RMSF and potential energy, which can nominate it as a 
      natural anti-inflammatory lead-compound candidate.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Ounissi, Mourad
AU  - Ounissi M
AD  - Laboratory of Ethnobotany and Natural Substances, Department of Natural Sciences, 
      ENS Kouba, BP.92, 16050, Algiers, Algeria; Department of Biology, Faculty of 
      Natural and Life Sciences, Ziane Achour University, BP.3117, Djelfa, Algeria. 
      Electronic address: ounissi_mourad@outlook.com.
FAU - Kameli, Abdelkrim
AU  - Kameli A
AD  - Laboratory of Ethnobotany and Natural Substances, Department of Natural Sciences, 
      ENS Kouba, BP.92, 16050, Algiers, Algeria.
FAU - Tigrine, Chafia
AU  - Tigrine C
AD  - Laboratory of Ethnobotany and Natural Substances, Department of Natural Sciences, 
      ENS Kouba, BP.92, 16050, Algiers, Algeria.
FAU - Rachedi, Fatma Zohra
AU  - Rachedi FZ
AD  - Department of Biology, Faculty of Natural and Life Sciences, Ziane Achour 
      University, BP.3117, Djelfa, Algeria.
LA  - eng
PT  - Journal Article
DEP - 20180704
PL  - England
TA  - Comput Biol Chem
JT  - Computational biology and chemistry
JID - 101157394
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Biological Products)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/chemical 
      synthesis/chemistry/*pharmacology
MH  - Biological Products/chemical synthesis/chemistry/*pharmacology
MH  - *Computer-Aided Design
MH  - Cyclooxygenase 2/*metabolism
MH  - Cyclooxygenase 2 Inhibitors/chemical synthesis/chemistry/*pharmacology
MH  - *Drug Evaluation, Preclinical
MH  - Humans
MH  - *Molecular Dynamics Simulation
MH  - Molecular Structure
MH  - Quantitative Structure-Activity Relationship
OTO - NOTNLM
OT  - COX-2
OT  - Lead compounds
OT  - Molecular dynamic simulation
OT  - Pharmacophore model
OT  - UNPD
OT  - Virtual screening
EDAT- 2018/09/09 06:00
MHDA- 2019/01/29 06:00
CRDT- 2018/09/09 06:00
PHST- 2018/04/21 00:00 [received]
PHST- 2018/06/22 00:00 [revised]
PHST- 2018/07/03 00:00 [accepted]
PHST- 2018/09/09 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
PHST- 2018/09/09 06:00 [entrez]
AID - S1476-9271(18)30157-9 [pii]
AID - 10.1016/j.compbiolchem.2018.07.005 [doi]
PST - ppublish
SO  - Comput Biol Chem. 2018 Dec;77:1-16. doi: 10.1016/j.compbiolchem.2018.07.005. Epub 
      2018 Jul 4.