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诺司卡品及其类似物作为化疗药物:最新进展

Noscapine and its Analogs as Chemotherapeutic Agent: Current updates.

作者信息

Tomar Vartika, Kukreti Shrikant, Prakash Satya, Madan Jitender, Chandra Ramesh

机构信息

Department of Chemistry, University of Delhi, Delhi - 110007, India.

出版信息

Curr Top Med Chem. 2017;17(2):174-188. doi: 10.2174/1568026616666160530153518.

Abstract

Recently, noscapine was reported as anticancer drug. Unlike, colchicine and podophyllotoxin, noscapine did not depolymerize microtubules even at stoichiometric concentrations but rather only mitigated their dynamics. Other microtubule-interacting chemotherapeutics, although quite effective, have therapy-limiting toxicities including immunosuppression and peripheral neuropathies. Recurrent cancers often become resistant. Noscapine however remains effective in some such instances, e.g., taxane-resistant ovarian cancer. Noscapine and analogs also do not show signs of neurotoxicity or immunosuppression. In addition, 9-bromo noscapine, Red-9-Br-Nos and other analogs were characterized for their structure and further studied in detail. On the other hand, noscapine was shown to be neuroprotective in mouse model of neurodegenerative disease and in stroke patients. Like low doses of colchicine, noscapine and its analog 9-Br-Noscapine also show anti-inflammatory activities. There are indications of a preventive use of noscapine in ischemiareperfusion injury and fibrosis. The entire biosynthetic pathway of noscapine is encoded as gene cluster within 401 kilo bases of genomic DNA, opening up opportunities for the large-scale biotechnological production of noscapine for medicinal needs. Thus, noscapine and its derivatives (noscapinoids) might be cost-effective and safe components for cancer chemotherapy. Owing to its low toxicity, it also might be useful for preventive use in high-risk situations. This brief review is an update of current research activity and patents on noscapine and its analogs.

摘要

最近,诺司卡品被报道为一种抗癌药物。与秋水仙碱和鬼臼毒素不同,即使在化学计量浓度下,诺司卡品也不会使微管解聚,而只是减轻其动态变化。其他与微管相互作用的化疗药物虽然相当有效,但具有限制治疗的毒性,包括免疫抑制和周围神经病变。复发性癌症往往会产生耐药性。然而,诺司卡品在某些情况下仍然有效,例如对紫杉烷耐药的卵巢癌。诺司卡品及其类似物也没有显示出神经毒性或免疫抑制的迹象。此外,对9-溴诺司卡品、Red-9-Br-Nos和其他类似物进行了结构表征并进一步详细研究。另一方面,在神经退行性疾病小鼠模型和中风患者中,诺司卡品被证明具有神经保护作用。与低剂量秋水仙碱一样,诺司卡品及其类似物9-溴诺司卡品也具有抗炎活性。有迹象表明诺司卡品可用于预防缺血再灌注损伤和纤维化。诺司卡品的整个生物合成途径被编码为基因组DNA 401千碱基内的基因簇,为大规模生物技术生产用于医疗需求的诺司卡品开辟了机会。因此,诺司卡品及其衍生物(诺司卡品类)可能是癌症化疗中具有成本效益且安全的成分。由于其低毒性,它也可能在高风险情况下用于预防。这篇简短的综述是关于诺司卡品及其类似物的当前研究活动和专利的最新情况。

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