scholarly journals Role of Vertex Index in Substructure Identification and Activity Prediction: A Study on Antitubercular Activity of a Series of Acid Alkyl Ester Derivatives

2014 ◽  
Vol 87 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Chandan Raychaudhury ◽  
Durga D. Kandel ◽  
Debnath Pal
Keyword(s):  
Antitubercular Activity ◽  
Alkyl Ester ◽  
Activity Prediction ◽  
Substructure Identification ◽  
Vertex Index

A Comparative Study of 1D Descriptors Supported CoMFA and CoMSIA QSAR Models to Gain Novel Insights into 1,2,4-Triazoles Acting As Antitubercular Agents

2020 ◽  
Vol 16 ◽  
Author(s):  
Rajdeep Ray ◽  
Gautham Shenoy ◽  
N V Ganesh Kumar Tummalapalli
Keyword(s):  
External Validation ◽  
Antitubercular Activity ◽  
New Drugs ◽  
Rational Approach ◽  
Antitubercular Drugs ◽  
Comfa Model ◽  
Qsar Models ◽  
Structural Insights ◽  
The Way

: Tuberculosis is one of the leading cause for deaths due to infectious disease worldwide. There is an urgent need for developing new drugs due to the rising incidents of drug resistance. Triazoles have previously been reported to show antitubercular activity. Various computational tools pave the way for a rational approach in understanding the structural importance of these compounds in inhibiting Mycobacterium tuberculosis growth. The aim of this study is to develop and compare two different QSAR models based on a set of previously reported molecules and use the best one for gaining structural insights in to the Triazole molecules. In the current study, two separate models were generated with CoMFA and CoMSIA descriptors respectively based on a dataset of triazole molecules showing antitubercular activity. Several one dimensional (1D) descriptors were added to each of the models and the validation results and the contour data generated from them were compared. The best model was studied to give a detailed understanding of the triazole molecules and their role in the antitubercular activity.The r2, q2, predicted r2 and SEP (Standard error of prediction) for the CoMFA model were 0.866, 0.573, 0.119 and 0.736 respectively and for the CoMSIA model the r2, q2, predicted r2 and SEP were calculated to be 0.998, 0.634, 0.013 and 0.869 respectively. Although both the QSAR models produced acceptable internal and external validation scores but the CoMSIA results were significantly better. The CoMSIA contours also provided a better match than CoMFA with most of the features of the active compound 30b. Hence, the CoMSIA model was chosen and its contours were explored for gaining structural insights on the triazole molecules. The CoMSIA contours helped us to understand the role of several atoms and groups of the triazole molecules in their biological activity. The possibilities for substitution in the triazole compounds that would enhance the activity were also analysed. Thus, this study paves the way for designing new antitubercular drugs in future.

scholarly journals Synthesis and study of spectrally diagnosed heterocyclic compound

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2613-2622
Author(s):  
Sajida. Munadi. Th.AL-Suraify ◽  
Mohammed Abdul-Mounther Othman
Keyword(s):  
Antibacterial Activity ◽  
Mycobacterium Tuberculosis ◽  
Antifungal Activity ◽  
Heterocyclic Compounds ◽  
Antitubercular Activity ◽  
Pharmacological Activities ◽  
Mycobacterium Tuberculosis H37rv ◽  
Clinical Utilization ◽  
General Terms

In general terms, medicinal chemistry manages the revelation & plan of recent remedial synthetic concoctions & its uses as meds. Throughout the most recent couple of decades, mixes bearing heterocyclic cores have gotten considerably more consideration of the scientific expert, because of their expansive chemo remedial exercises, for example, calming, anthelmintic, hostile to tubercular, against parasitic & hostile to microbial exercises. Furthermore, Heterocycles & medicines are both interred related, the human is totally dependent on drugs & most of the drugs are derived from heterocyclic compounds. Hetero cycles & their derivatives have been excited regards chemist mainly due to broad-spectrum chemical & pharmacological activities. Most of the heterocyclic compounds are naturally occurs & playing the important role of metabolism regards cells of living. There has been a bigger count of pharmacologically attracted compounds of heterocyclic, several of which have been under continues clinical utilization. This paper presented a detailed study of synthesis which is spectrally detected Heterocyclic compounds, in results described the antibacterial activity of (e)-s-4-(is nicotinamide)-5-(phenoxymethyl)-4h-1, 2, 4-triazol-3-yl 3-(substituted phenyl) prop-2- enethioate. (7a-7f) and antifungal activity of (e)-s-4-(isonicotinamido)-5-(phenoxymethyl)-4h-1, 2, 4-triazol-3-yl 3-(substituted phenyl) prop-2-enethioate. (7a-7f), antitubercular activity of against mycobacterium tuberculosis h37rv presented the scope of this paper.

scholarly journals Therapeutic Potential of Curcumin as an Antimycobacterial Agent

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1278
Author(s):  
Nilakshi Barua ◽  
Alak Kumar Buragohain
Keyword(s):  
Therapeutic Potential ◽  
Curcuma Longa ◽  
Chemical Properties ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Clinical Investigations ◽  
Tuberculosis Therapy ◽  
Synthetic Derivatives ◽  
Vast Range

Curcumin is the principal curcuminoid obtained from the plant Curcuma longa and has been extensively studied for its biological and chemical properties. Curcumin displays a vast range of pharmacological properties, including antimicrobial, anti-inflammatory, antioxidant, and antitumor activity. Specifically, curcumin has been linked to the improvement of the outcome of tuberculosis. There are many reviews on the pharmacological effects of curcumin; however, reviews of the antitubercular activity are comparatively scarcer. In this review, we attempt to discuss the different aspects of the research on the antitubercular activity of curcumin. These include antimycobacterial activity, modulation of the host immune response, and enhancement of BCG vaccine efficacy. Recent advances in the antimycobacterial activity of curcumin synthetic derivatives, the role of computer aided drug design in identifying curcumin targets, the hepatoprotective role of curcumin, and the dosage and toxicology of curcumin will be discussed. While growing evidence supports the use of curcumin and its derivatives for tuberculosis therapy, further preclinical and clinical investigations are of pivotal importance before recommending the use of curcumin formulations in public health.

scholarly journals Solid Lipid Nanoparticles as Formulative Strategy to Increase Oral Permeation of a Molecule Active in Multidrug-Resistant Tuberculosis Management

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1132
Author(s):  
Antonella Obinu ◽  
Elena Piera Porcu ◽  
Sandra Piras ◽  
Roberta Ibba ◽  
Antonio Carta ◽  
...  
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Oral Absorption ◽  
Antitubercular Activity ◽  
Multidrug Resistant ◽  
Lipid Nanoparticles ◽  
Particle Size Range ◽  
Solid Lipid ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

The role of mycobacterial efflux pumps in drug-resistant tuberculosis has been widely reported. Recently, a new compound, named SS13, has been synthesized, and its activity as a potential efflux inhibitor has been demonstrated. In this work, the chemical–physical properties of the SS13 were investigated; furthermore, a formulative study aimed to develop a formulation suitable for oral administration was performed. SS13 shows nonintrinsic antitubercular activity, but it increases the antitubercular activity of all the tested drugs on several strains. SS13 is insoluble in different simulated gastrointestinal media; thus, its oral absorption could be limited. Solid lipid nanoparticles (SLNs) were, therefore, developed by using two different lipids, Witepsol and/or Gelucire. Nanoparticles, having a particle size (range of 200–450 nm with regards to the formulation composition) suitable for intestinal absorption, are able to load SS13 and to improve its permeation through the intestinal mucosa compared to the pure compound. The cytotoxicity is influenced by the concentration of nanoparticles administered. These promising results support the potential application of these nanocarriers for increasing the oral permeation of SS13 in multidrug-resistant tuberculosis management.

The role of different sampling methods in improving biological activity prediction using deep belief network

2016 ◽  
Vol 38 (4) ◽  
pp. 195-203 ◽  
Author(s):  
Fahimeh Ghasemi ◽  
Afshin Fassihi ◽  
Horacio Pérez-Sánchez ◽  
Alireza Mehri Dehnavi
Keyword(s):  
Biological Activity ◽  
Sampling Methods ◽  
Deep Belief Network ◽  
Activity Prediction ◽  
Belief Network

Strategically Placed Trifluoromethyl Substituent in the Realm of Antitubercular Drug Design

2019 ◽  
Vol 14 (2) ◽  
pp. 114-123 ◽  
Author(s):  
Sidhartha S. Kar ◽  
Cinu A. Thomas
Keyword(s):  
Drug Design ◽  
Phenyl Ring ◽  
Antitubercular Activity ◽  
Trifluoromethyl Group ◽  
Antitubercular Agents ◽  
Antitubercular Drug ◽  
Pharmacokinetic Properties ◽  
Prime Objective ◽  
Electron Withdrawing Group

Background:Fluorinated substituents have played, and continue to play an important role in antitubercular drug design. Nonetheless, previous works have indicated that organofluorines like –F, CF3, -OCF3, and CHF2 etc have been used to modulate the pharmacodynamic and pharmacokinetic behaviour of antitubercular agents. Among the fluorinated groups, trifluoromethyl (-CF3) substituent is a very familiar pharmacophore used widely in antitubercular research.Objective:This review assesses the development of selected trifluoromethyl group bearing antitubercular agents that are either in treatment or considered to be potential. The prime objective of the present investigation was to provide initial evidences for the hypothesis that addition of trifluoromethyl group to antiTB agents could improve their potency. We also aimed to contribute to a better understanding of the role of trifluoromethyl group on drug-likeness antitubercular activity.Methods:In this review, we first brief out the possible effect of –CF3 substituent on pharmacodynamic and pharmacokinetic properties of drugs. Next, we turn to emphasize on the effect of trifluoromethyl substituent on different antitubercular scaffolds. Finally, we open the topic for the researchers to design potential antitubercular agents suitably substituted with fluorinated groups.Results:This review suggests that the replacement of –CF3 group in heterocyclic as well as phenyl ring led to the improvement in pharmacodynamic and pharmacokinetic properties of the compounds. Hence it's not surprising to see –CF3 group emerging as an alternative electron withdrawing group instead of halogens in many promising antitubercular agents.Conclusion:This unusual spectrum of advantage allied with its lipophilicity enhancing effect, made –CF3 group distinct from other substituents in modern antitubercular drug design. The present study provides conceptual advances to the understanding of the physicochemical properties of –CF3 group and its effect on antitubercular activity.

Bioinformatics and Computer Simulation approaches to the discovery and analysis of Bioactive Peptides

2022 ◽  
Vol 23 ◽  
Author(s):  
Zhang Shuli ◽  
Liu Linlin ◽  
Gao Li ◽  
Zhao Yinghu ◽  
Shi Nan ◽  
...  
Keyword(s):  
Computer Simulation ◽  
Computer Aided Design ◽  
Bioactive Peptides ◽  
New Technologies ◽  
Simulation Methods ◽  
Activity Prediction ◽  
Correlation Models ◽  
Traditional Process ◽  
Aided Design

Abstract: The traditional process of separating and purifying bioactive peptides is laborious and time-consuming. Using a traditional process to identify is difficult, and there is a lack of fast and accurate activity evaluation methods. How to extract bioactive peptides quickly and efficiently is still the focus of bioactive peptides research. In order to improve the present situation of the research, bioinformatics techniques and peptidome methods are widely used in this field. At the same time, bioactive peptides have their own specific pharmacokinetic characteristics, so computer simulation methods have incomparable advantages in studying the pharmacokinetics and pharmacokinetic-pharmacodynamic correlation models of bioactive peptides. The purpose of this review is to summarize the combined applications of bioinformatics and computer simulation methods in the study of bioactive peptides, with focuses on the role of bioinformatics in simulating the selection of enzymatic hydrolysis and precursor proteins, activity prediction, molecular docking, physicochemical properties, and molecular dynamics. Our review shows that new bioactive peptide molecular sequences with high activity can be obtained by computer-aided design. The significance of the pharmacokinetic-pharmacodynamic correlation model in the study of bioactive peptides is emphasized. Finally, some problems and future development potential of bioactive peptides binding new technologies are prospected.

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