Heterocyclic Compounds as Hsp90 Inhibitors: A Perspective on Anticancer Applications

Abstract

Heat shock proteins (Hsps) have garnered special attention in cancer therapy as molecular chaperones with regulatory/mediatory effects on folding, maintenance/stability, maturation, and conformation of proteins as well as their effects on prevention of protein aggregation. Hsp90 ensures the stability of various client proteins needed for the growth of cells or the survival of tumor cells; therefore, they are overexpressed in tumor cells and play key roles in carcinogenesis. Accordingly, Hsp90 inhibitors are recognized as attractive therapeutic agents for investigations pertaining to tumor suppression. Natural Hsp90 inhibitors comprising geldanamycin (GM), reclaimed analogs of GM including 17-AAG and DMAG, and radicicol, a natural macrocyclic antifungal, are among the first potent Hsp90 inhibitors. Herein, recently synthesized heterocyclic compounds recognized as potent Hsp90 inhibitors are reviewed along with the anticancer effects of heterocyclic compounds, comprising purine, pyrazole, triazine, quinolines, coumarin, and isoxazoles molecules.

Natural and Synthetic Inhibitors of Heat Shock Protein 90 Chaperone in Cancer Treatment

“…However, MB differs from GA at C-6 (methyl in MB and methoxy in GA), C-11 (methoxy in MB and hydroxy in GA) and a methoxy group at C-15 (instead of at C-17 of GA). 23 Co-crystal structures revealed the hydrogen bonding between carbamate group of MB directly with Asp79, Gly83 and indirectly via water molecules with Leu34 and Thr171 of HSP90.…”

“…HB is a C-11,15, dimethoxy 17-desmethoxy analog of GA (Figure 2C). 23 Similar to GA, HB also binds to the N-terminal ATP-binding pocket of the HSP90. HB exhibited activity against both the parental as well as drug-resistant MCF7 cell lines.…”

Synthesis and anti-proliferative activity of dehydroabietinol derivatives bearing a triazole moiety

“…14,15 Heterocyclic compounds are an important class of organic compounds that have been widely used for many important medicinal and synthetic chemistry applications. [16][17][18][19] In particular, the privileged 1,2,3-triazole scaffold has drawn considerable attention due to its favourable properties, such as moderate dipole character, hydrogen bonding capability, rigidity and stability under in vivo conditions. 20 1,2,3-Triazole derivatives display a variety of pharmacological properties such as antibacterial, 21,22 antimalarial, 23 antitubercular 24 and antiviral 25 activity.…”

N-Heterocyclic Analogs: A New Prospect in Cancer Therapy

“…In affluent and opulent countries, carcinoma is the leading cause of fatality. Mutation in the DNA can be an important cause of cancer development, which may be of heredity or adoption, genetic and epigenetic both factors concerned [13][14][15][16]. There are hormonal and many different epigenetic factors responsible for the promotion of malignancy and even alteration by the suppression of the oncogenes for the proliferation of cancer cells [17][18][19][20].…”