Development and in vivo evaluation of fused benzazole analogs of anti-melanoma agent HA15

Future Med Chem. 2021 Jul;13(14):1157-1173. doi: 10.4155/fmc-2021-0001. Epub 2021 Jun 7.


Background: In line with our recent discovery of an efficient anticancer thiazolebenzenesulfonamide framework HA15 (1) based on a remarkable endoplasmic reticulum stress inducement mode of action, we report herein a series of innovative constrained HA15 analogs, featuring four types of bicylic derivatives. Results: The structure-activity relationship analysis, using a cell line assay, led us to identify a novel version of HA15: a new benzothiazole derivative (10b) exhibiting important anti-melanoma effect against sensitive and resistant melanoma cells. Meanwhile, compound 10b induced a significant tumor growth inhibition in vivo with no apparent signs of toxicity. Conclusion: These results consistently open new directions to improve and develop more powerful anticancer therapeutics harboring this type of fused framework.

Keywords: HA15; anti-melanoma agent; antineoplastic activity; benzazole derivatives; mice xenografts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Benzothiazoles / chemistry*
  • Benzothiazoles / pharmacology
  • Benzothiazoles / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Endoplasmic Reticulum Stress / drug effects
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Mice
  • Mice, Nude
  • Structure-Activity Relationship
  • Transplantation, Heterologous


  • Antineoplastic Agents
  • Benzothiazoles