Discovery and Development of Lead Compounds from Natural Sources Using Computational Approaches

2015 ◽  
pp. 455-475 ◽  
Author(s):  
José L. Medina-Franco
Keyword(s):  
Natural Sources ◽  
Computational Approaches ◽  
Lead Compounds

scholarly journals Chemical Constituents from the Fruits ofForsythia suspensaand Their Antimicrobial Activity

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ping-Chung Kuo ◽  
Guo-Feng Chen ◽  
Mei-Lin Yang ◽  
Ya-Hua Lin ◽  
Chi-Chung Peng
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Column Chromatography ◽  
Chemical Constituents ◽  
Phenylethanoid Glycosides ◽  
Natural Sources ◽  
Methanol Extracts ◽  
Lead Compounds ◽  
Forsythia Suspensa ◽  
First Time

Lignans and phenylethanoid glycosides purified fromForsythia suspensawere reported to display various bioactivities in the previous literature, including the antimicrobial activity. Therefore, the present research is aimed to purify and identify the chemical constituents of the methanol extracts of fruits ofF. suspensa. The methanol extracts of fruits ofF. suspensawere fractionated and further purified with the assistance of column chromatography to afford totally thirty-four compounds. Among these isolates, 3β-acetoxy-20α-hydroxyursan-28-oic acid (1) was reported from the natural sources for the first time. Some of the purified principles were subjected to the antimicrobial activity examinations againstEscherichia colito explore new natural lead compounds.

Structure and Function of L,D- and D,D-Transpeptidase Family Enzymes from Mycobacterium tuberculosis

2020 ◽  
Vol 27 (19) ◽  
pp. 3250-3267 ◽  
Author(s):  
Gideon F. Tolufashe ◽  
Victor T. Sabe ◽  
Colins U. Ibeji ◽  
Thandokuhle Ntombela ◽  
Thavendran Govender ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bacterial Cell ◽  
Structure And Function ◽  
New Drugs ◽  
Computational Studies ◽  
Computational Approaches ◽  
Lead Compounds ◽  
And Function ◽  
Enzymatic Mechanisms

Peptidoglycan, the exoskeleton of bacterial cell and an essential barrier that protects the cell, is synthesized by a pathway where the final steps are catalysed by transpeptidases. Knowledge of the structure and function of these vital enzymes that generate this macromolecule in M. tuberculosis could facilitate the development of potent lead compounds against tuberculosis. This review summarizes the experimental and computational studies to date on these aspects of transpeptidases in M. tuberculosis that have been identified and validated. The reported structures of L,D- and D,D-transpeptidases, as well as their functionalities, are reviewed and the proposed enzymatic mechanisms for L,D-transpeptidases are summarized. In addition, we provide bioactivities of known tuberculosis drugs against these enzymes based on both experimental and computational approaches. Advancing knowledge about these prominent targets supports the development of new drugs with novel inhibition mechanisms overcoming the current need for new drugs against tuberculosis.

scholarly journals Molecular Modeling Applied to the Discovery of New Lead Compounds for P2 Receptors Based on Natural Sources

2020 ◽  
Vol 11 ◽  
Author(s):  
Anael Viana Pinto Alberto ◽  
Natiele Carla da Silva Ferreira ◽  
Rafael Ferreira Soares ◽  
Luiz Anastacio Alves
Keyword(s):  
Molecular Modeling ◽  
P2 Receptors ◽  
Natural Sources ◽  
Lead Compounds

scholarly journals Bioautography with TLC-MS/NMR for Rapid Discovery of Anti-tuberculosis Lead Compounds from Natural Sources

2016 ◽  
Vol 2 (4) ◽  
pp. 294-301 ◽  
Author(s):  
Edyta M. Grzelak ◽  
Changhwa Hwang ◽  
Geping Cai ◽  
Joo-Won Nam ◽  
Mary P. Choules ◽  
...  
Keyword(s):  
Natural Sources ◽  
Lead Compounds

Therapeutic Targets and Computational Approaches on Drug Development for COVID-19

2020 ◽  
Vol 20 (24) ◽  
pp. 2210-2220 ◽  
Author(s):  
Anusuya Shanmugam ◽  
Nisha Muralidharan ◽  
Devadasan Velmurugan ◽  
M. Michael Gromiha
Keyword(s):  
Drug Development ◽  
Computational Methods ◽  
Drug Repurposing ◽  
World Health ◽  
Short Peptides ◽  
Computational Approaches ◽  
Lead Compounds ◽  
The World ◽  
Health Organization ◽  
Approved Drugs

World Health Organization declared coronavirus disease (COVID-19) caused by SARS coronavirus-2 (SARS-CoV-2) as pandemic. Its outbreak started in China in Dec 2019 and rapidly spread all over the world. SARS-CoV-2 has infected more than 800,000 people and caused about 35,000 deaths so far, moreover, no approved drugs are available to treat COVID-19. Several investigations have been carried out to identify potent drugs for COVID-19 based on drug repurposing, potential novel compounds from ligand libraries, natural products, short peptides, and RNAseq analysis. This review is focused on three different aspects; (i) targets for drug design (ii) computational methods to identify lead compounds and (iii) drugs for COVID-19. It also covers the latest literature on various hit molecules proposed by computational methods and experimental techniques.

scholarly journals Insecticidal Pregnane Glycosides from the Root Barks of Periploca sepium

2016 ◽  
Vol 11 (10) ◽  
pp. 1934578X1601101
Author(s):  
Renfeng Li ◽  
Ximei Zhao ◽  
Baojun Shi ◽  
Shaopeng Wei ◽  
Jiwen Zhang ◽  
...  
Keyword(s):  
Insecticidal Activity ◽  
2D Nmr ◽  
Positive Control ◽  
Botanical Pesticides ◽  
Natural Sources ◽  
Lead Compounds ◽  
Pregnane Glycoside ◽  
Periploca Sepium ◽  
Insecticidal Activities

To explore novel lead compounds for botanical pesticides from natural sources, a new pregnane glycoside (periplocoside) P2 as well as its isomer, a known pregnane glycoside P1, were isolated from the root barks of Periploca sepium using a bioactivity-guided method, and their structures were confirmed by 1D NMR, 2D NMR, IR, ESI-MSn and HRMS. Their insecticidal activities were evaluated against 3rd instar larvae of M. separata, and the results indicated that P2 exhibited excellent insecticidal activity with LC50 values of 2.9 and 2.2 mg/mL after 24 and 48 h, respectively, much lower than those of the positive control celangulin-V (24.7 and 21.0 mg/mL after 24 and 48 h, respectively). This work demonstrated that pregnane glycosides from Periploca sepium could be promising lead compounds for developing botanical pesticides urgently needed in agriculture.

scholarly journals In-silico design of novel myocilin inhibitors for glaucoma therapy

2017 ◽  
Vol 16 (10) ◽  
pp. 2527-2533
Author(s):  
Min Tang ◽  
Yang Fu ◽  
Ying Fan ◽  
Ming-Shui Fu ◽  
Zhi Zheng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Binding Energies ◽  
Computational Approaches ◽  
Screening Technique ◽  
Lead Compounds ◽  
Potent Inhibition ◽  
Pharmacokinetic Properties ◽  
Molecular Libraries

Purpose: To explore newer computational approaches in the design of novel myocilin inhibitors for the treatment of glaucoma.Methods: An in-silico virtual screening technique based on simulation of molecular docking was utilised to design a novel myocilin inhibitors for the treatment of  glaucoma. The designed novel molecules were theoretically evaluated to predict their pharmacokinetic properties and toxic effects. Lead molecules were screened out in virtual screening technique on the basis of low binding energies obtained in AutoDock based molecular docking simulation.Results: Out of ten top lead compounds screened, ZINC01729523 and ZINC04692015 were promising, having shown potent inhibition of myocilin, good pharmacokinetic properties and absence of any toxic effects.Conclusion: In-silico virtual screening of molecular libraries containing a large number of ligands is very useful for short-listing of potential lead molecules for further structure-based discovery of antiglaucoma-drugs.Keywords: Glaucoma, Myocilin, Docking, Virtual-screening, Autodock, Ligand, Drug design

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