Hexafluoroisopropanol-Mediated Domino Reaction for the Synthesis of Thiazolo-androstenones: Potent Anticancer Agents

Abstract

A cascade reaction of thioamides with 6β-bromoandrostenedione in hexafluoroisopropanol formed substituted thiazolo-androstenones. This is a simple and mild protocol to synthesize novel molecules by using readily available reagents and substrates. Feasibility of the reaction has been rationalized by density functional theory calculations. Moreover, these compounds are potent growth inhibitors of colon, central nervous system, melanoma, ovarian, and renal cancer cell lines with 50% growth inhibition values as low as 1.04 μM.

Synthesis of Hydrazone Derivatives of 4-[4-Formyl-3-(2-oxochromen-3-yl)pyrazol-1-yl]benzoic acid as Potent Growth Inhibitors of Antibiotic-resistant Staphylococcus aureus and Acinetobacter baumannii

“…In our quest to develop novel methodologies to synthesize bioactive molecules [23,24,25,26], we have reported the synthesis of novel pyrazole derivatives as potent antimicrobial agents [27,28,29]. Based on our lead molecules and known pharmacological properties of coumarin derivatives, we designed the novel molecules hoping to produce potent antimicrobial agents (Figure 1).…”

Synthesis and Antimicrobial Studies of 4-[3-(3-Fluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic Acid and 4-[3-(4-Fluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic Acid as Potent Growth Inhibitors of Drug-Resistant Bacteria

“…In our pursuit to find novel small-molecule heterocycles, 11−15 we have reported the synthesis and antimicrobial activities of several pyrazole-derived hydrazones. 16−19 Based on our reported molecules, we designed and synthesized fluorine-substituted aldehydes to synthesize hydrazone derivatives for antimicrobial studies.…”

Antimelanoma activities of chimeric thiazole–androstenone derivatives

“…2,4-Dimethyl substituted derivative ( 7 ) is a potent growth inhibitor of all the tested cell lines of the melanoma panel. Among all the reported thiobenzamide-derived thiazoles [16], only 3-fluorophenyl derivative ( 8 ) showed significant activity against the melanoma panel.

Figure 2Thiazole containing androstenone derivatives as potent anti-melanoma agents.

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“…In our effort to develop new methodologies to synthesize bioactive compounds [11][12][13][14], we have synthesized a number of thiazole and thiazolo-androstenone derivatives [15][16][17]. We submitted 50 of the synthesized thiazole-androstenone derivatives to the National Cancer Institute (NCI) Development Therapeutics Program (DTP) to test against 60 cancer cell lines (https://dtp.cancer.gov/).…”

“…Based on these data, we found a very promising structure–activity relationship of these molecules against melanoma cell lines. Overall, amino-thiazole derivatives ( table 1 , 1 – 7 ) [ 15 ] were more toxic to melanoma cell lines than phenyl thiazole derivatives ( 8 ) [ 16 ]. Fluoro and oxy (hydroxy and methoxy) derivatives were the potent growth inhibitors of the tested cancer cell lines.…”