《Identification and optimization of biphenyl derivatives as novel tubulin inhibitors targeting colchicine-binding site overcoming multidrug resistance》 was written by Cheng, Bao; Zhu, Guirong; Meng, Linghua; Wu, Guolin; Chen, Qin; Ma, Shengming. Reference of 1-Bromo-3,4,5-trimethoxybenzeneThis research focused ontubulin optimization biphenyl colchicine multidrug resistance; Anticancer activity; Biphenyl derivatives; Multidrug resistance; Tubulin inhibitors. The article conveys some information:
Microtubule targeting agents (MTAs) are among the most successful chemotherapeutic drugs, but their efficacy is often limited by the development of multidrug resistance (MDR). Therefore, the development of novel MTAs with the ability to overcome MDR is urgently needed. In this contribution, through modification of the unsym. biaryl compounds, we discovered a novel compound dxy-1-175 with potent anti-proliferative activity against cancer cells. Mechanistic study revealed that dxy-1-175 inhibited tubulin polymerization by interacting with the colchicine-binding site of tubulin, which caused cell cycle arrest at G2/M phase. Based on the predicted binding model of dxy-1-175 with tubulin, a series of new 4-benzoylbiphenyl analogs were designed and synthesized. Among them, the hydrochloride compound 12e with improved solubility and good stability in human liver microsome, exhibited the most potent anti-proliferative activity with IC50 value in the low nanomolar range, and markedly inhibited the growth of breast cancer 4T1 xenograft in vivo. Notably, 12e effectively overcame P-gp-mediated MDR and our preliminary data suggested that 12e may not be a substrate of P-glycoprotein (P-gp). Taken together, our study reveals a novel MTA 12e targeting the colchicine-binding site with potent anticancer activity and the ability to circumvent MDR. In addition to this study using 1-Bromo-3,4,5-trimethoxybenzene, there are many other studies that have used 1-Bromo-3,4,5-trimethoxybenzene(cas: 2675-79-8Reference of 1-Bromo-3,4,5-trimethoxybenzene) was used in this study.
1-Bromo-3,4,5-trimethoxybenzene(cas: 2675-79-8) is an important raw material and intermediate used in organic synthesis, pharmaceuticals, agrochemicals and dyestuff.Reference of 1-Bromo-3,4,5-trimethoxybenzene1-Bromo-3,4,5-trimethoxybenzene can be used to synthesize analogs of HA14-1, which shows promising anticancer properties.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary