{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T23:33:53Z","timestamp":1776814433937,"version":"3.51.2"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,12,27]],"date-time":"2017-12-27T00:00:00Z","timestamp":1514332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In an attempt to develop potent antitumor agents, new 1,3,4-thiadiazole derivatives were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the K562 chronic myelogenous leukemia cell line that expresses the Bcr-Abl tyrosine kinase. N-(5-Nitrothiazol-2-yl)-2-((5-((4-(trifluoromethyl)phenyl)amino)-1,3,4-thiadiazol-2-yl)thio)acetamide (2) inhibited the Abl protein kinase with an IC50 value of 7.4 \u00b5M and showed selective activity against the Bcr-Abl positive K562 cell line. Furthermore, a Bcr-Abl-compound 2 molecular modelling simulation highlighted the anchoring role of the nitrothiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. These results provide promising starting points for further development of novel kinase inhibitors.<\/jats:p>","DOI":"10.3390\/molecules23010059","type":"journal-article","created":{"date-parts":[[2017,12,27]],"date-time":"2017-12-27T11:16:00Z","timestamp":1514373360000},"page":"59","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Design, Synthesis, and Biological Evaluation of Novel 1,3,4-Thiadiazole Derivatives as Potential Antitumor Agents against Chronic Myelogenous Leukemia: Striking Effect of Nitrothiazole Moiety"],"prefix":"10.3390","volume":"23","author":[{"given":"Mehlika","family":"Alt\u0131ntop","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eski\u015fehir 26470, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Halil","family":"Ciftci","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan"},{"name":"Stanford PULSE Institute, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9220-2659","authenticated-orcid":false,"given":"Mohamed","family":"Radwan","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan"},{"name":"Department of Chemistry of Natural Compounds, National Research Center, Dokki, 12622 Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4847-9711","authenticated-orcid":false,"given":"Belgin","family":"Sever","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eski\u015fehir 26470, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2252-0923","authenticated-orcid":false,"given":"Zafer","family":"Kaplanc\u0131kl\u0131","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eski\u015fehir 26470, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taha","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan"},{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoko","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikako","family":"Fujita","sequence":"additional","affiliation":[{"name":"Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masami","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0280-5550","authenticated-orcid":false,"given":"Ahmet","family":"\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eski\u015fehir 26470, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.bpa.2013.10.010","article-title":"The Global Burden of Cancer","volume":"27","author":"Popat","year":"2013","journal-title":"Best Pract. 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