Advancements and Challenges in Tuberculosis Drug Discovery: A Comprehensive Overview DOI
Puja Kumari Agnivesh, Arnab Roy,

Shashikanta Sau

et al.

Microbial Pathogenesis, Journal Year: 2024, Volume and Issue: 198, P. 107074 - 107074

Published: Nov. 7, 2024

Language: Английский

Design, synthesis and biological evaluation of novel pyrido-[2,3-d]-pyrimidin-2-amine analogues as antimycobacterial agents DOI

Boddupalli Venkata Siva Kumar,

Yogesh Mahadu Khetmalis,

Kosana Sai Chaitanya

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1303, P. 137600 - 137600

Published: Jan. 18, 2024

Language: Английский

Citations

5
The progress of Mycobacterium tuberculosis drug targets DOI Creative Commons
Xin Zhang,

R Zhao,

Yao Qi

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Oct. 21, 2024

Tuberculosis (TB) has been troubling humans for hundreds of years, is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, Mtb can infect almost all organs the body and one deadly diseases in world. At present, first-line treatment regimen long cycle prone to multiple drug resistance. Anti-tuberculosis drugs latent infection (LTBI) resistance are increasing year year, new targets bioactive compounds urgently needed treat this disease. This review focuses on latest reported anti-TB related recent reviews current TB major defects, outlines key developed date Mtb, situation newly discovered resistant forms drugs. To provide reference research development bring strategies patients.

Language: Английский

Citations

4
In silico elucidation and network pharmacology analysis of phytochemicals from Elephantorrhiza elephantina and Pentanisia prunelloides for antitubercular activity DOI

Alaiha Zaheen,

Pinki Francina Lefalo,

Sanchaita Rajkhowa

et al.

Gene Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102155 - 102155

Published: Jan. 1, 2025

Language: Английский

Citations

0
Computational approaches: atom-based 3D-QSAR, molecular docking, ADME-Tox, MD simulation and DFT to find novel multi-targeted anti-tubercular agents DOI Creative Commons
Debadash Panigrahi, Susanta Kumar Sahu

BMC Chemistry, Journal Year: 2025, Volume and Issue: 19(1)

Published: Feb. 13, 2025

Tuberculosis (TB) has become the biggest threat to human society because of rapid rise in resistance causative bacteria Mycobacterium tuberculosis (MTB) against available anti-tubercular drugs. There is an urgent need design new multi-targeted agents overcome species MTB through computational tools. With this aim mind, we performed a combination atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR), six-point pharmacophore (AHHRRR), and molecular docking analysis on series fifty-eight agents. The created QSAR model had R2 value 0.9521, Q2 0.8589, Pearson r-factor 0.8988, all which are statistically significant. This means that was effective at making predictions. We study for data set compounds with two important target proteins, Enoyl acyl carrier protein reductase (InhA) (PDBID: 2NSD) Decaprenyl phosphoryl-β-D-Ribose 20-epimerase (DprE1) 4FDO). used similarity search principle do virtual screening 237 from PubChem database order find strong act multiple targets. screened compound, MK3, showed highest score −9.2 −8.3 kJ/mol towards both proteins InhA DprE1, were picked 100 ns molecular-dynamic simulation using GROMACS. compound MK3 thermodynamically stable effectively bound their active binding pockets without much movement. occupied orbital (HOMO), lowest unoccupied (LUMO), energy gap predicts reactivity stability identified molecule. Based result above studies, proposed can be successfully development novel agent high affinity favourable ADME-T properties.

Language: Английский

Citations

0
Molecular docking, free energy calculations, ADMETox studies, DFT analysis, and dynamic simulations highlighting a chromene glycoside as a potential inhibitor of PknG in Mycobacterium tuberculosis DOI Creative Commons
Muharib Alruwaili, Tilal Elsaman, Magdi Awadalla Mohamed

et al.

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 25, 2025

Tuberculosis (TB), caused by the Mycobacterium tuberculosis (M.tb), remains a serious medical concern globally. Resistant M.tb strains are emerging, partly because can survive within alveolar macrophages, resulting in persistent infection. Protein kinase G (PknG) is mycobacterial virulence factor that promotes survival of macrophages. Targeting PknG could offer an opportunity to suppress resistant strains. In present study, multiple computational tools were adopted screen library 460,000 molecules for potential inhibitors M.tb. Seven Hits (1-7) identified with binding affinities exceeding reference compound (AX20017) towards catalytic domain. Next, ADMETox studies performed identify best hit appropriate drug-like properties. The chromene glycoside (Hit 1) was as inhibitor better pharmacokinetic and toxicity profiles rendering it drug candidate. Furthermore, quantum analysis conducted assess mechanical electronic properties Hit 1, providing guidance further studies. Molecular dynamics simulations also 1 against PknG, confirming stability its complex. sum, findings current study highlight lead development drugs capable treating TB.

Language: Английский

Citations

0
Nanoenabling MbtI Inhibitors for Next-Generation Tuberculosis Therapy DOI Creative Commons
Giulia Cazzaniga, Matteo Mori, Anna Griego

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

The urgent need for safer and innovative antitubercular agents remains a priority the scientific community. In pursuit of this goal, we designed evaluated novel 5-phenylfuran-2-carboxylic acid derivatives targeting Mycobacterium tuberculosis (Mtb) salicylate synthase (MbtI), key enzyme, absent in humans, that plays crucial role Mtb virulence. Several potent MbtI inhibitors demonstrating significant activity favorable safety profile were identified. Structure-guided optimization yielded 5-(3-cyano-5-isobutoxyphenyl)furan-2-carboxylic (1e), which exhibited strong inhibition (IC50 = 11.2 μM) promising vitro (MIC99 32 μM against M. bovis BCG). Esters 1e effectively loaded into poly(2-methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA) polymersomes (POs) delivered to intracellular mycobacteria, resulting reduced viability. This study provides foundation use POs development future MbtI-targeted therapies tuberculosis.

Language: Английский

Citations

0
Role of guanylate-binding protein 5 in inflammatory diseases, immune diseases, cancers, and its potential therapeutic implications DOI

Xufan Sun,

Guiyuan Jin, Huihui Zhou

et al.

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Language: Английский

Citations

0
Role of vesicular nanocarriers for the treatment of tuberculosis DOI
Brojendra Nath Saren, Sayali Dighe, Saroj Kumar Jha

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 99 - 145

Published: Jan. 1, 2025

Language: Английский

Citations

0
Drug repurposing for bacterial infections DOI
Mahnoor Ilyas,

Muhammad Saad Latif,

Alvina Gul

et al.

Progress in molecular biology and translational science, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 21

Published: Jan. 1, 2024

Language: Английский

Citations

2
Artificial intelligence in drug discovery: A new frontier in the fight against Mycobacterium tuberculosis DOI

Mohammad Abavisani,

Alireza Khoshrou, Amirhossein Sahebkar

et al.

Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(3), P. 103909 - 103909

Published: Feb. 1, 2024

Language: Английский

Citations

1