OMICS International Research Article
Drug Designing: Open Access
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ISSN: 2169-0138
Bassyouni et al., Drug Des 2017, 6:2
DOI: 10.4172/2169-0138.1000148
Volume 6 • Issue 2 • 1000148
Drug Des, an open access journal
ISSN: 2169-0138
Keywords: Molecular modeling; Co-crystallized ligand; Scoring
functions; Optimization; Molecular Operating Environment MOE;
Drug design
Introduction
Te application of molecular modeling approaches for drug
discovery is provided for novel therapeutic targets for drug discovery.
Molecular modeling is a technique providing the energy of interaction
between two molecules; this approach has several recent methods used
recently in pharmaceutical applications and drug discovery [1]. It is
used to allow the binding afnity of small molecule candidate drugs
to their protein targets in order to improve the afnity and activity
of small molecules. Molecular modeling techniques are powerful in
elucidating the diferent physical, chemical and biological properties of
large molecules and interactions [2,3]. In recent years, new drugs are
developed from a process of trial phases in the procedure, including
several computer systems developed depend on the design based on
the structure of the protein and the targets are used to discover new
candidates for therapeutic applications [4-9].
In addition, the physical and chemical properties of the synthesized
compounds are derived from oxadiazole as antibacterial, anti-
Trypanosoma cruzi and antifungal using the molecular modeling
techniques that leads to more biological activity [10]. On the other
hand, the quantitative structure-activity relationship (3D-QSAR)
based on both the pharmacophore and the docking alignments. Tis
method has been used successfully to assist in the design of new small
molecule candidates and to investigate the mechanism of ligand-protein
interaction [11,12].
Materials and Methods
In the present study the tested compounds 1, 3, 8, 9, 10 and 12 were
allowed; 3D conformations and reduction of the energy to be minimized
were determined using ChemBioOfce V12 and Merifom Merck
*Corresponding author: Fatma Bassyouni, Chemistry of Natural and Microbial
Products Department, National Research Centre, Cairo, Egypt, Tel: 020-
01118596967; E-mail: fatma.nrc@hotmail.com
Received April 06, 2017; Accepted June 07, 2017; Published June 14, 2017
Citation: Bassyouni F, El Hefnawi M, El Rashed A, Rehim MA (2017) Molecular
Modeling and Biological Activities of New Potent Antimicrobial, Anti-Infammatory
and Anti-Nociceptive of 5-Nitro Indoline-2-One Derivatives. Drug Des 6: 148. doi:
10.4172/2169-0138.1000148
Copyright: © 2017 Bassyouni F, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original
author and source are credited.
Molecular Modeling and Biological Activities of New Potent Antimicrobial,
Anti-Inflammatory and Anti-Nociceptive of 5-Nitro Indoline-2-One
Derivatives
Fatma Bassyouni
1
*, Mahmoud El Hefnawi
2
, Ahmed El Rashed
1
and Mohamed Abdel Rehim
3
1
Department of Chemistry of Natural and Microbial Products, National Research Centre, Dokki, Cairo, Egypt
2
Informatics and Systems Department, National Research Centre, Cairo, Egypt
3
Department of Analytical Chemistry, Stockholm University, Stockholm, Sweden
Abstract
In recent years, molecular modeling has become an important technique for drug discovery and pharmaceutical
science. The objective of this study is to determine the molecular modeling of the antibacterial, anti-infammatory
and anti-nociceptive activities of a new series of pyrazoles, oxadiazoles and sugar hydrazines of 5-nitroindolin-2-
one derivatives. The molecular modeling protocol was applied using the MOE (Molecular Operating Environment)
software. Synthetic compounds 1, 3, 8, 9, 10 and 12 were the most active compounds, as antibacterial, anti-
infammatory and anti-nociceptive activities were studied for the binding affnity of the cyclooxygenase1 (COX1),
The glucocorticoid receptor (GR), the cytochrome P450 receptor of 14alfa-sterol demethylases (CYP51) and
the dihydroprotease synthase receptor. Molecular modeling studies revealed that the [(methylbenzyl)-5-nitro-2-
oxoindolin-3-ylideneamino-benzohydrazide derivative (3) gave a score of (-15.8587 kcal/mol), while 1,3,4-oxadiazol-
2-yl) phenylimino)-1-(methylbenzyl)-5-nitroindolin-2-one derivative (9) gave a higher score (-16.8038 kcal/mol)
than fucanazole Co-crystallized gave a score of (-10.2837 kcal/mol). However, the compound (12), D-Arabinose-
(methylbenzyl)-5-nitro-2-oxoindolin-(3-ylideneamino) hydrazone derivative gave a score of (-24.6577 kcal/mol)
greater than the co-crystallized ligand which gave a score of (-16.6717 kcal/mol).
Molecular Force Field function, with a maximum number of iterations
of 500 and a minimum of 0.1 RMS gradients [13]. Te PharmMapper
service was used to predict targets based on the Pharmaparget db
database containing 7000 pharmacophores based on a set of 1500 drug
targets [14]. Te procedure was followed using the standard protocol set
on SurFlex-dock and the geometry of the result was studied using the
SurFlex-dock Pose Viewer installation.
Tis study aims to model the optimization of the tested compounds
for more potent inhibitors using the protocol steps that was developed
by the MOE operating environment sofware [15] and to reducing
the minimum energy of the tested compounds in the feld of the
fmmf-Hamiltonian-Force94x, followed by systematic conformational
research (RMS gradient 0.01), the best 30 were stored in the database
format (PDB2Oye) [16].
Active site Finder tool of MOE was used to identify and
calculate active sites in the receptor molecule from the 3D atomic
coordinates of the receptor. By default, all calculated sites were
appeared as selected. Before the docking a database of these ligands
was prepared using MOE.. Tese sites were refned with the help of the
global handheld from the preliminary docking of the tested compounds,