4'-Alkoxyl substitution enhancing the anti-mitotic effect of 5-(3',4',5'-substituted)anilino-4-hydroxy-8-nitroquinazolines as a novel class of anti-microtubule agents.
Mitosis inhibitors are powerful anticancer drugs. Based on a novel anti-microtubule agent of 5-(4'-methoxy)anilino-4-hydroxy-8-nitroquinazoline, a series of 5-(3',4',5'-substituted)anilino-4-hydroxy-8- nitroquinazolines were designed and synthesized to investigate the effect of the substitution on the inhibitory activity against mitotic progression of tumor cells. The large alkoxyl substitution on the 4'-position of 5-anilino ring is beneficial for the potency. The 5-(3',4',5'-trimethoxy)anilino-8-nitroquinazoline (1h) displays an overwhelming activity in arresting the cells at the G2/M phase, providing a promising new template for further development of potent microtubule-targeted anti-mitotic drugs.
Jin
Yi
Y
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Zhou
Zu-Yu
ZY
Tian
Wei
W
Yu
Qiang
Q
Long
Ya-Qiu
YQ
D000438:Alcohols / Q000737:chemistry*; D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D050256:Antimitotic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects* / Q000502:physiology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000438:Alcohols; D000814:Aniline Compounds; D050256:Antimitotic Agents; D011799:Quinazolines; C059688:alkoxyl radical