一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Briefings in bioinformatics >>article
Briefings in bioinformatics

Briefings in bioinformatics

IF: 7.7
Download PDF

Machine learning–enabled virtual screening indicates the anti-tuberculosis activity of aldoxorubicin and quarfloxin with verification by molecular docking, molecular dynamics simulations, and biological evaluations

Published:22 November 2024 DOI: 10.1093/bib/bbae696 PMID: 39737570
Si Zheng,?Yaowen Gu,?Yuzhen Gu,?Yelin Zhao,?Liang Li,?Min Wang,?Rui Jiang,?Xia Yu,?Ting Chen,?Jiao Li

Abstract

Drug resistance in Mycobacterium tuberculosis (Mtb) is a significant challenge in the control and treatment of tuberculosis, making efforts to combat the spread of this global health burden more difficult. To accelerate anti-tuberculosis drug discovery, repurposing clinically approved or investigational drugs for the treatment of tuberculosis by computational methods has become an attractive strategy. In this study, we developed a virtual screening workflow that combines multiple machine learning and deep learning models, and 11?576 compounds extracted from the DrugBank database were screened against Mtb. Our screening method produced satisfactory predictions on three data-splitting settings, with the top predicted bioactive compounds all known antibacterial or anti-TB drugs. To further identify and evaluate drugs with repurposing potential in TB therapy, 15 screened potential compounds were selected for subsequent computational and experimental evaluations, out of which aldoxorubicin and quarfloxin showed potent inhibition of Mtb strain H37Rv, with minimal inhibitory concentrations of 4.16 and 20.67?μM/mL, respectively. More inspiringly, these two compounds also showed antibacterial activity against multidrug-resistant TB isolates and exhibited strong antimicrobial activity against Mtb. Furthermore, molecular docking, molecular dynamics simulation, and the surface plasmon resonance experiments validated the direct binding of the two compounds to Mtb DNA gyrase. In summary, our effective comprehensive virtual screening workflow successfully repurposed two novel drugs (aldoxorubicin and quarfloxin) as promising anti-Mtb candidates. The verification results provide useful information for the further development and clinical verification of anti-TB drugs.

Substances (54)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Sunitinib 557795-19-4 C22H27FN4O2 459 suppliers Inquiry
Sunitinib 557795-19-4 C22H27FN4O2 459 suppliers Inquiry
Sunitinib 557795-19-4 C22H27FN4O2 459 suppliers Inquiry
Sunitinib 557795-19-4 C22H27FN4O2 459 suppliers Inquiry
NVP-LDE225 956697-53-3 C26H26F3N3O3 210 suppliers Inquiry
NVP-LDE225 956697-53-3 C26H26F3N3O3 210 suppliers Inquiry
NVP-LDE225 956697-53-3 C26H26F3N3O3 210 suppliers Inquiry
NVP-LDE225 956697-53-3 C26H26F3N3O3 210 suppliers Inquiry
AZD8931 848942-61-0 C23H25ClFN5O3 178 suppliers $34.00-$35050.00
AZD8931 848942-61-0 C23H25ClFN5O3 178 suppliers $34.00-$35050.00

Similar articles

IF:3.6

Virtual Screening and Biological Evaluation of Natural Products as Novel VPS34 Inhibitors that Modulate Autophagy

ChemMedChem Xiaowen Feng, Baoming Wu,etc Published: 22 November 2024
IF:3.2

Targeted isolation of lignans and triterpenoids from kadsura coccinea by molecular networking and anti-RA-FLS activity

Phytochemistry Shi-qi Liu, Qing-ling Xie,etc Published: 27 November 2024
IF:2.3

Use of a molecular beacon based fluorescent method for assaying uracil DNA glycosylase (Ung) activity and inhibitor screening

Biochemistry and Biophysics Reports Avani Mehta , Prateek Raj ,etc Published: 1 July 2021
河北区| 疏勒县| 汉阴县| 菏泽市| 永仁县| 凤台县| 集贤县| 恭城| 永康市| 缙云县| 哈巴河县| 岑溪市| 潞西市| 津南区| 磴口县| 齐齐哈尔市| 阜新市| 平昌县| 大名县| 若羌县| 新竹市| 茌平县| 华阴市| 林甸县| 沁阳市| 屏东县| 虎林市| 凤山县| 肇东市| 韶关市| 揭东县| 神木县| 筠连县| 图木舒克市| 陆川县| 龙南县| 井陉县| 左云县| 西城区| 称多县| 大关县|