Antimelanoma activities of chimeric thiazole–androstenone derivatives

Abstract

The discovery of chimeric anti-melanoma agents is reported. These molecules are potent growth suppressors of melanoma cells in vitro with growth inhibition of 50% (GI 50 ) values as low as 1.32 µM. Compounds were more toxic to melanoma cells in vitro than commonly used anti-melanoma agent dacarbazine as measured by TUNEL assay. They induced both caspase-independent apoptosis evident by colocalization of TUNEL with endonuclease G (EndoG) and caspase-mediated apoptosis measured by colocalization of TUNEL with caspase-activated DNase (CAD). In addition, compounds 3 and 5 strongly induced oxidative injury to melanoma cells as measured by TUNEL colocalization with heme oxygenase-1 (HO1). Dacarbazine induced only caspase-independent apoptosis, which may explain why it is less cytotoxic to melanoma cells than compounds 3 , 4 and 5 .

Domino Reaction Protocol to Synthesize Benzothiophene-Derived Chemical Entities as Potential Therapeutic Agents

“…In our quest to find antibacterial and antineoplastic agents, ,− we tested these novel benzothiophene compounds against several strains of Gram-positive and Gram-negative bacterial strains. To our delight, we found several compounds with potent activity against Gram-positive bacteria and A.…”

Efficient Synthesis of Thiazole-Fused Bisnoralcohol Derivatives as Potential Therapeutic Agents

“… 14 We have found thiazole-fused androstenones ( 1 ) and ethisterones ( 2 ) as potent growth inhibitors of cancer cell lines including melanoma and renal cancer cell line panels. 15 Thiazole-fused nootkatones (e.g., 3 ) are found to be potent growth inhibitors of drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). 16 Encouraged by these results, we envisaged the synthesis of fused thiazole-bisnoralcohol derivatives as potential cytotoxic agents and these compounds will be less lipophilic than androstenone and ethisterone derivatives.…”

Synthesis, molecular docking, and biological evaluation of [3,2-b]indole fused 18β-glycyrrhetinic acid derivatives against skin melanoma

“…Therefore, there is a need to identify the novel selective anti-melanoma molecules with minimal side effects that can be used to treat melanoma skin cancers. 4 Treatment of different types of cancer with different terpenoid class of natural products including oleanolic acid, betulinic acid, ursolic acid and glycyrrhetinic acid has become a major focus due to their potent chemotherapeutic activities 5 (Fig. 1).…”

“…Therefore, there is a need to identify the novel selective anti-melanoma molecules with minimal side effects that can be used to treat melanoma skin cancers. 4 …”