{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:39:22Z","timestamp":1780339162553,"version":"3.54.1"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82204347"],"award-info":[{"award-number":["82204347"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82473778"],"award-info":[{"award-number":["82473778"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Undergraduate Student Innovation and Practice Incubation Base Project of Naval Medical University","award":["FH2024166"],"award-info":[{"award-number":["FH2024166"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Cancer persists as a leading concern in the current medical field, and current therapies are limited by toxicity, cost, and resistance. Targeted inhibition of tubulin polymerization is considered as a promising therapeutic strategy for cancer treatment. Methods: Thirty-one new tubulin polymerization inhibitors were designed via molecular hybridization techniques, and BLI technology was employed to quantitatively investigate their interactions with tubulin. Antiproliferative activities against MCF-7, MDA-MB-231, A549, and HeLa cell lines was evaluated using the CCK8 assay. Apoptosis induction and cell cycle arrest were analyzed by flow cytometry. The anti-tumor activity of compound B6 was validated in a mouse melanoma tumor model. Results: Compounds exhibited varying degrees of antiproliferative activity against four tumor cell lines. Among them, compound B6 was the most promising candidate and displayed strong broad-spectrum anticancer activity with an average IC50 value of 2 \u03bcM. The mechanism studies revealed that compound B6 inhibited tubulin polymerization in vitro, disrupted cell microtubule networks, and arrested the cell cycle at G2\/M phase. Furthermore, B6 displayed significant in vivo antitumor efficacy in a melanoma tumor model with tumor growth inhibition rates of 70.21% (50 mg\/kg). Conclusions: This work shows that B6 is a promising lead compound deserving further investigation as a potential anticancer agent.<\/jats:p>","DOI":"10.3390\/ph19010161","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T08:08:21Z","timestamp":1768550901000},"page":"161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Discovery of New Quinazolinone and Benzimidazole Analogs as Tubulin Polymerization Inhibitors with Potent Anticancer Activities"],"prefix":"10.3390","volume":"19","author":[{"given":"Boye","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China"},{"name":"School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"PLA Naval Medical Center, Second Military Medical University, Shanghai 200052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6760-5045","authenticated-orcid":false,"given":"Conghao","family":"Gai","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Song","sequence":"additional","affiliation":[{"name":"PLA Naval Medical Center, Second Military Medical University, Shanghai 200052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingguo","family":"Meng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9688-9091","authenticated-orcid":false,"given":"Xiaoyun","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s10555-020-09883-w","article-title":"FOXO transcription factor family in cancer and metastasis","volume":"39","author":"Jiramongkol","year":"2020","journal-title":"Cancer Metast. 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