{'fraction_non_alphanumeric': 0.04479371316306483, 'fraction_numerical': 0.02082514734774067, 'mean_word_length': 5.7, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 1, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Synthesis of Anti‐Microtubule N‐(2‐Arylindol‐7‐yl)benzenesulfonamide Derivatives and Their Antitumor Mechanisms

Prostate cancer is one of the most common cancers in men worldwide, and its incidence has increased even in the last few years. Clinically, patients with prostate cancer initially respond effectively to androgen depletion therapy, which induces apoptosis of tumor cells. However, androgen depletion therapy becomes ineffective in most patients after a period of time. In these hormone-refractory prostate cancer cases, tumors become metastatic and patient mortality is high. As apoptosis-resistant prostate cancer is resistant to conventional chemotherapeutic drugs, it is necessary to develop novel agents for the treatment of HRPC. Microtubules are a promising target for anticancer drug development. Anti-microtubule drugs perturb the dynamics of microtubules, and consequently arrest cell cycle progression and induce apoptosis. Clinically, anti-microtubule drugs have shown potent activity in the treatment of patients with HRPC. 7] Development of a new generation of antimicrotubule drugs is still ongoing, with the goal of improving efficacy and safety. 9] Combretastatin A4 and its derivatives not only show excellent antitumor efficacy but also exhibit antiangiogenesis activity. N-{2-[(4-Hydroxyphenyl)amino]-3-pyridinyl}-4-methoxybenzenesulfonamide (I, E7010, also called ABT-571) and its analogues (Figure 1) are demonstrated to have potent antitumor activity against drug-resistant tumor cell lines both in vitro and in vivo. E7010 binds to the colchicine binding site of tubulin and consequently inhibits tubulin polymerization, and blocks mitosis. 19] Ring connection of E7010 yields N-(2-chloroindol-7-yl)-4-methoxybenzenesulfonamide (II), which retains antimitotic activity. However, structure–activity relationship studies have demonstrated that structural alterations result in different antitumor mechanisms. N-(3-Chloroindol-7-yl)-1,4-benzenedisulfonamide (IV, E7070) induces cell-cycle arrest at the G1 and/or G2 phase. [11, 13] Alteration of the 2-chloroindole derivative II results in the corresponding 3-chloroindole derivative III. Interestingly, compound III exhibits the dual functions of II and IV. Both substitutions on the C4 position of benzenesulfonamide and on the indole ring affect antitumor mechanisms. Herein we report a series of N-(2-arylindol-7-yl)benzenesulfonamide derivatives and the antitumor mechanism of the most potent compound, N-(2-phenylindol-7-yl)-4-methoxybenzenesulfonamide (2).