Vinca alkaloids and analogues as anti-cancer agents: Looking back, peering ahead

Bioorg Med Chem Lett. 2018 Sep 15;28(17):2816-2826. doi: 10.1016/j.bmcl.2018.06.044. Epub 2018 Jun 25.

Abstract

Cancer still represents a "nightmare" worldwide, causing annually millions of victims. Several antiproliferative molecules are currently used as drugs market and offer a pharmaceutical opportunity for attenuating and treating tumor manifestations. In this context, natural sources have a relevant role, since they provide the 60% of currently-used anticancer agents. Among the numerous natural products, acting via different mechanisms of action, microtubule-targeting agents (MTAs) have a high therapeutic potential, since they disrupt the abnormal cancer cell growth, interfering with the continuous mitotic division. Vinca alkaloids (VAs) are the earliest developed MTAs and approved for clinical use (Vincristine, Vinblastine, Vinorelbine, Vindesine, and Vinflunine) as agents in the treatment of hematological and lymphatic neoplasms. Here, we review the state-of-art of VAs, discussing their mechanism of action and pharmacokinetic properties and highlighting their therapeutic relevance and toxicological profile. Additionally, we briefly disclosed the technological approaches faced so far to ameliorate the pharmacological properties, as well as to avoid the drug resistance. Lastly, we introduced the recent advances in the discovery of new derivatives.

Keywords: Antimitotic agents; Emerging vinblastine-related compounds; Microtubule-targeting agents; Vinca alkaloids.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Cell Proliferation / drug effects
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Vinca Alkaloids / chemistry
  • Vinca Alkaloids / therapeutic use*

Substances

  • Antineoplastic Agents
  • Vinca Alkaloids