Combretastatins A-4 and A-1 and their derivatives: Review

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Abstract

This modern literature review covers the results of study of the tubulin inhibitors, mainly combretastatins A-4 and A-1 (CA-4 and CA-1) or colhicinoids. The article presents data of SAR (Structure Activity Relation) study of numerous CA-4 analogues as well as mechanisms of their action evaluated in vitro (using cultured tumor cells) and in vivo (using animals with transplanted murine tumors or with xenografts of human tumors of various histogenesis). The phosphate CA-4 derivative (CA-4P) is characterized as a vascular disrupting agent (VDAs). Approaches are described for developing CA-4 analogues stable in cis-configuration as well as methods for enhancing hydrophility of promising derivatives along with retention of their high cytotoxicity. The results of various clinical trials both of CA-4P and CA-1P administered individually or in combination with chemotherapeutic drugs are also presented. Our conclusion is that despite numerous studies performed during the last thirty years no ideal water-soluble molecule with stable cis-configuration and high cytotoxic activity has been obtained which could become the basis of an active anti-tumor medicine.

The aim of the review is to present the systematic data on antitumor activity of combretastatin CA-4 and CA-1 analogues as well as the modes of their modification and therapeutic usage.

About the authors

E. R. Nemtsova

Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre, Ministry of Health of Russia

Author for correspondence.
Email: nemtz@yandex.ru
ORCID iD: 0000-0002-3579-1733

Elena R. Nemtsova, 

3, 2nd Botkinskiy pr., Moscow, 125284.

Russian Federation

N. B. Morozova

Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre, Ministry of Health of Russia

ORCID iD: 0000-0002-7159-805X

Natalia B. Morozova, 

3, 2nd Botkinskiy pr., Moscow, 125284.

Russian Federation

A. D. Plyutinskaya

Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre, Ministry of Health of Russia

ORCID iD: 0000-0002-6898-2931

Anna D. Plyutinskaya, 

3, 2nd Botkinskiy pr., Moscow, 125284.

Russian Federation

A. N. Noev

Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre, Ministry of Health of Russia

ORCID iD: 0000-0003-2245-4946

Alexey N. Noev, 

3, 2nd Botkinskiy pr., Moscow, 125284.

Russian Federation

A. A. Pankratov

Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre, Ministry of Health of Russia

ORCID iD: 0000-0001-7291-9743

Andrey A. Pankratov, 

3, 2nd Botkinskiy pr., Moscow, 125284.

Russian Federation

P. V. Shegay

Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre, Ministry of Health of Russia

ORCID iD: 0000-0001-9755-1164

Peter V. Shegay,

3, 2nd Botkinskiy pr., Moscow, 125284.

Russian Federation

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