Tubulin inhibitors: an insight into new strategies to combat leukemia.

Abstract

Leukemia is a type of cancer that affects the blood and bone marrow and characterized by the uncontrolled production and accumulation of blood cells. According to the World Health Organization (WHO), leukemia is among the fifteen most commonly diagnosed cancers worldwide and the eleventh leading cause of mortality. Tyrosine kinase inhibitors are the first-line choice for the treatment of acute or chronic leukemia. However, mutations in tyrosine kinase proteins are the major cause of resistance. Therefore, the discovery of new targeted antileukemic molecules is essential for the treatment of leukemia. Amongst the various tyrosine kinase inhibitors, tubulin inhibitors displayed promising results in preventing the proliferation of cancer cells. Microtubule targeting agents (MTAs) bind with tubulin protein and affect their functionalities in leukemia cells. In this context, recently reported antileukemic tubulin inhibitors viz., synthetic, natural, dual/multi-inhibitors, antibody-drug conjugates etc. have been summarized (2018 to present) in this manuscript. Structure activity relationship (SAR) analysis depicted that the presence of trimethoxy phenyl, chalcone, quinoline, and oxadiazole scaffolds improved the tubulin inhibitory activity against acute lymphoblastic leukemia. The present review also reported the recent patents and clinical trial data related to antileukemic tubulin inhibitors.