{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T18:50:05Z","timestamp":1788288605723,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2022R25"],"award-info":[{"award-number":["PNURSP2022R25"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["RGP.1\/346\/43"],"award-info":[{"award-number":["RGP.1\/346\/43"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"publisher","award":["PNURSP2022R25"],"award-info":[{"award-number":["PNURSP2022R25"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"publisher","award":["RGP.1\/346\/43"],"award-info":[{"award-number":["RGP.1\/346\/43"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>We describe the design and synthesis of two isatin-tethered quinolines series (Q6a\u2013h and Q8a\u2013h), in connection with our research interest in developing novel isatin-bearing anti-tubercular candidates. In a previous study, a series of small molecules bearing a quinoline-3-carbohydrazone moiety was developed as anti-tubercular agents, and compound IV disclosed the highest potency with MIC value equal to 6.24 \u00b5g\/mL. In the current work, we adopted the bioisosteric replacement approach to replace the 3,4,5-trimethoxy-benzylidene moiety in the lead compound IV with the isatin motif, a privileged scaffold in the TB drug discovery, to furnish the first series of target molecules Q6a\u2013h. Thereafter, the isatin motif was N-substituted with either a methyl or benzyl group to furnish the second series Q8a\u2013h. All of the designed quinoilne-isatin conjugates Q6a\u2013h and Q8a\u2013h were synthesized and then biologically assessed for anti-tubercular actions towards drug-susceptible, MDR, and XDR strains. Superiorly, the N-benzyl-bearing compound Q8b possessed the best activities against the examined M. tuberculosis strains with MICs equal 0.06, 0.24, and 1.95 \u00b5g\/mL, respectively.<\/jats:p>","DOI":"10.3390\/molecules27248807","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T06:11:01Z","timestamp":1670825461000},"page":"8807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Development of Novel Isatin-Tethered Quinolines as Anti-Tubercular Agents against Multi and Extensively Drug-Resistant Mycobacterium tuberculosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4205-0538","authenticated-orcid":false,"given":"Mohamed A.","family":"Abdelrahman","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadia","family":"Almahli","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarfah","family":"Al-Warhi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taghreed A.","family":"Majrashi","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa M.","family":"Abdel-Aziz","sequence":"additional","affiliation":[{"name":"The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo 11651, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-4017","authenticated-orcid":false,"given":"Wagdy M.","family":"Eldehna","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt"},{"name":"School of Biotechnology, Badr University in Cairo, Cairo 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-0084","authenticated-orcid":false,"given":"Mohamed A.","family":"Said","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112821","DOI":"10.1016\/j.ejmech.2020.112821","article-title":"Phenanthrolinic analogs of quinolones show antibacterial activity against M. tuberculosis","volume":"207","author":"Coulibaly","year":"2020","journal-title":"Eur. 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