{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Singh V"],"funding":["National Institute of Allergy and Infectious Diseases","Department of Science and Innovation, South Africa","NIAID NIH HHS","Welch Foundation","University of Cape Town","Bill and Melinda Gates Foundation","South African Medical Research Council"],"pagination":["2315-2326"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9673142"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(11)"],"pubmed_abstract":["Alternative mode-of-inhibition of clinically validated targets is an effective strategy for circumventing existing clinical drug resistance. Herein, we report 1,3-diarylpyrazolyl-acylsulfonamides as potent inhibitors of HadAB/BC, a 3-hydroxyl-ACP dehydratase complex required to iteratively elongate the meromycolate chain of mycolic acids in <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>). Mutations in compound <b>1</b>-resistant <i>Mtb</i> mutants mapped to HadC (Rv0637; K157R), while chemoproteomics confirmed the compound's binding to HadA (Rv0635), HadB (Rv0636), and HadC. The compounds effectively inhibited the HadAB and HadBC enzyme activities and affected mycolic acid biosynthesis in <i>Mtb</i>, in a concentration-dependent manner. Unlike known 3-hydroxyl-ACP dehydratase complex inhibi"],"journal":["ACS infectious diseases"],"pubmed_title":["1,3-Diarylpyrazolyl-acylsulfonamides Target HadAB/BC Complex in <i>Mycobacterium tuberculosis</i>."],"pmcid":["PMC9673142"],"funding_grant_id":["P01AI095208","OPP1095631","A-0015","AI130929","P01 AI095208","OPP1066878","R21 AI130929","AI153477","R21 AI153477"],"pubmed_authors":["Alfonso S","Liu J","Jackson M","Sanz O","Muller R","Grzegorzewicz AE","Lee RE","Krieger IV","Ghorpade SR","Sacchettini JC","Chibale K","Bantscheff M","Ghidelli-Disse S","Khonde LP","Angala B","Drewes G","Ioerger TR","Fienberg S","Urones B","Singh V"],"additional_accession":[]},"is_claimable":false,"name":"1,3-Diarylpyrazolyl-acylsulfonamides Target HadAB/BC Complex in <i>Mycobacterium tuberculosis</i>.","description":"Alternative mode-of-inhibition of clinically validated targets is an effective strategy for circumventing existing clinical drug resistance. Herein, we report 1,3-diarylpyrazolyl-acylsulfonamides as potent inhibitors of HadAB/BC, a 3-hydroxyl-ACP dehydratase complex required to iteratively elongate the meromycolate chain of mycolic acids in <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>). Mutations in compound <b>1</b>-resistant <i>Mtb</i> mutants mapped to HadC (Rv0637; K157R), while chemoproteomics confirmed the compound's binding to HadA (Rv0635), HadB (Rv0636), and HadC. The compounds effectively inhibited the HadAB and HadBC enzyme activities and affected mycolic acid biosynthesis in <i>Mtb</i>, in a concentration-dependent manner. Unlike known 3-hydroxyl-ACP dehydratase complex inhibi","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2026-05-28T07:03:04.957Z","creation":"2025-02-19T04:20:11.656Z"},"accession":"S-EPMC9673142","cross_references":{"pubmed":["36325756"],"doi":["10.1021/acsinfecdis.2c00392"]}}