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Objectives
The search for new TB drugs has become one of the great challenges for modern medicinal chemistry. An improvement in the outcomes of TB chemotherapy can be achieved by the development of new, shorter, cheap, safe and effective anti-TB regimens.
Methods
Chalcones (1a-1o) were synthesized and evaluated for their antimycobacterial activity...
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This work used quantum chemical method via DFT to calculate molecular descriptors for the development of QSAR model to predict bioactivity (IC50- 50% inhibition concentration) of the selected 1, 2, 3-triazole-pyrimidine derivatives against receptor (human gastric cancer cell line, MGC-803). The selected molecular parameters were obtained by B3LYP...
Citations
... Anagani et al. have synthesized and evaluated in vitro antimycobacterial activity of chalcone derivatives against Mycobacterium bovis BCG using growth inhibition assays. 60 In an attempt to synthesize designed compounds, 3,4-dimethoxybenzaldehyde reacted with various substituted acetophenones by the Claisen-Schmidt condensation as shown in Scheme 13. Moreover, the mode of action of compounds XXIII was screened by mycolic acid methyl esters and fatty acid methyl esters analysis using TLC methods. ...
... Chalcones, also known as 1,3-diaryl-2-propen-1-ones, are flavonoids that consist of open-chain flavonoids with two aromatic rings connected by a three-carbon a, b-unsaturated carbonyl. The radical dousing capacity of several Chalcones due to the presence of phenolic groups has increased interest in using these compounds or their derivatives as food preservatives or pharmaceuticals (Anagani et al., 2020;Gomes et al., 2017;Gupta & Jain, 2015;L opez et al., 2001). The ancient medicinal application of Chalcones is known to be associated with the use of several-year-old herbs and plants for the treatment of various medical conditions. ...
Tuberculosis (TB) is a serious infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). The World Health Organization (WHO) estimates that 1.8 million people die each year from TB, with 10 million new cases being registered each year. In this study, 50 Chalcones were developed, five of which were synthesized, and their inhibitory effects against Mtb were studied. The discovery of new powerful inhibitors with IC 50 values in the sub-micro molar range resulted from the development of structure-activity relationships (SAR). The goal of the molecular modelling studies was to uncover the most important structural criteria underpinning the binding affinity and selectivity of this class of inhibitors as possible anti-TB drugs. Because of their great efficacy and selectivity, our developed nitro and benzyloxy substituted Chalcones compounds appear to be promising anti-TB therapies. ARTICLE HISTORY
Chalcones have various biological effects, from immune boosting to anti-cancer and anti-diabetic. Structurally modified chalcones (SMC) are clinically relevant for diabetes and cardiometabolic complications. From the original research articles, a structurally proven and biologically outstanding 14 structurally modified chalcones were screened and inducted in this study. This study evaluated the effects of SMC towards diabetes via network pharmacology analysis. The network data shows compounds S2, S3, S5, S9 &S12 suit the diabetes target. Especially Compounds S5 and S9 have a higher binding affinity towards the targets of TNF, PI3K, MAPK1 and AKT1 active sites. Compound S9 [(E)-3-(4-(1H-imidazol-1-yl)phenyl)-1-(4-(2,4-difluorobenz-yloxy)phenyl)prop-2-en-1-one] have identified with stronger binding affinities towards the active sites of MAPK3 (PDB:4QTB) -10.5(Kcal/mol). To provide a more effective mechanism for demonstrating protein-ligand interaction, one of the molecular docking complex (ERK2 kinase-S5) was subjected to a molecular dynamic at 300K for 100 ns. In term of structural stability, structure compactness, residual flexibility and hydrogen bond interaction of the complex was evaluated Integrating network pharmacology, in silico virtual screening, and molecular docking analysis shows that structurally modified compounds are effective and may help identify lead compounds towards glycemic control.Communicated by Ramaswamy H. Sarma.
A series of halogenated chalcone derivatives were designed and developed for anti-tubercular activity. Novel molecules were designed and in-silico screening were performed using admetSAR, SwissADME, and Osiris Property Explorer. From the initial filter the top 10 compounds were docked using the Autodock tool 1.5.6. and the binding energies of the docked compounds were higher than the standard drugs Isoniazid.and Ethionamide. Based on the in-silico and docking results, the top halogenated chalcones were synthesized and characterized using FT-IR, mass spectrometry, 1H, and 13C NMR spectroscopy. The chalcones were further evaluated for anti-tubercular activity using MABA against the H37Rv strain. Among the series of compounds, DK12 and DK14 showed potent in-vitro activity, with MICs of 0.8 µg/ml, in comparison with 1.6 µg/ml of the first-line drug Isoniazid. Further molecular dynamics simulations studies for 100 ns revealed that the key interaction with TYR 158 were observed in both DK12 and DK14 in the InhA active site. The compound DK12 further showed significant interactions with PHE 149 and ARG 153 residues and is a hit molecule among the series. Further DK12 and DK14 does not show any significance toxicity. The compounds DK12 needs to be optimized and further investigation to be carried out against InhA.Communicated by Ramaswamy H. Sarma.
Cases of drug-resistant tuberculosis (TB) have increased worldwide in the last few years, and it is a major threat to global TB control strategies and the human population. Mycobacterium tuberculosis is a common causative agent responsible for increasing cases of TB and as reported by WHO, approximately, 1.5 million death occurred from TB in 2020. Identification of new therapies against drug-resistant TB is an urgent need to be considered primarily. The current investigation aims to find the potential biogenic chalcone against the potential targets of drug-resistant TB via in silico approach. The ligand library of biogenic chalcones was screened against DprE1. Results of molecular docking and in silico ADMET prediction revealed that ZINC000005158606 has lead-like properties against the targeted protein. Pharmacophore modeling was done to identify the pharmacophoric features and their geometric distance present in ZINC000005158606. The binding stability study performed using molecular dynamics (MD) simulation of the DprE1-ZINC000005158606 complex revealed the conformational stability of the complex system over 100 ns with minimum deviation. Further, the in silico anti-TB sensitivity of ZINC000005158606 was found to be higher as compared to the standards against Mycobacterium tuberculosis. The overall in silico investigation indicated the potential of identified hit to act as a lead molecule against Mycobacterium tuberculosis.Graphical Abstract
Medicinal chemists around the world have been inspired by nature and have successfully extracted chemicals from plants. Research on enzymatic modifications of naturally occurring compounds has played a critical role in the search for biologically active molecules to treat diseases. This book explores compounds of interest to researchers and clinicians. It presents a comprehensive analysis about the medicinal chemistry (drug design, structure-activity relationships, permeability data, cytotoxicity, appropriate statistical procedures, and molecular modeling studies) of different compounds. Each chapter brings contributions from known scientists explaining experimental results which can be translated into clinical practice. Each chapter follows a specific format for a phytochemical agent with common chemical features: General background on the (phyto)chemistry of the scaffold General background on the pharmacological profile of the scaffold A Description of the proposed derivatives and their advantages with respect to the parent compounds (emphasizing the synthetic approaches and structure-activity relationships) In silico analysis of the crucial interactions with the biological target Clinical studies and patent survey (if available) on the new and proposed structures The objective of this book set is to fulfil gaps in currently acquired knowledge with information from the recent years. It serves as a guide for academic and professional researchers and clinicians.
Medicinal chemists around the world have been inspired by nature and have successfully extracted chemicals from plants. Research on enzymatic modifications of naturally occurring compounds has played a critical role in the search for biologically active molecules to treat diseases. This book explores compounds of interest to researchers and clinicians. It presents a comprehensive analysis about the medicinal chemistry (drug design, structure-activity relationships, permeability data, cytotoxicity, appropriate statistical procedures, and molecular modeling studies) of different compounds. Each chapter brings contributions from known scientists explaining experimental results which can be translated into clinical practice. Each chapter follows a specific format for a phytochemical agent with common chemical features: General background on the (phyto)chemistry of the scaffold General background on the pharmacological profile of the scaffold A Description of the proposed derivatives and their advantages with respect to the parent compounds (emphasizing the synthetic approaches and structure-activity relationships) In silico analysis of the crucial interactions with the biological target Clinical studies and patent survey (if available) on the new and proposed structures The objective of this book set is to fulfil gaps in currently acquired knowledge with information from the recent years. It serves as a guide for academic and professional researchers and clinicians.
Tuberculosis (TB) is a serious infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). The World Health Organization (WHO) estimates that 1.8 million people die each year from TB, with 10 million new cases being registered each year. In this study, 50 Chalcones were developed, five of which were synthesized, and their inhibitory effects against Mtb were studied. The discovery of new powerful inhibitors with IC50 values in the sub-micro molar range resulted from the development of structure–activity relationships (SAR). The goal of the molecular modelling studies was to uncover the most important structural criteria underpinning the binding affinity and selectivity of this class of inhibitors as possible anti-TB drugs. Because of their great efficacy and selectivity, our developed nitro and benzyloxy substituted Chalcones compounds appear to be promising anti-TB therapies.
Communicated by Ramaswamy H. Sarma
