Synthesis of quinone-based heterocycles of broad-spectrum anticancer activity

Abstract

A synthesis of benzo[ e][1,2,4]triazines and 1,2,4-triazolospiro[4,5]deca-2,6,9-trien-8-ones has been developed from reactions of amidrazones with 2-chloro-1,4-benzoquinone in EtOAc containing 0.5 mL of piperidine. This highly regioselective and one-pot process provided rapid access to 1,2,4-triazolospiro[4,5]deca-2,6,9-trien-8-ones (60%–70%) and benzo[ e][1,2,4]triazines (11%–18%). On reacting amidrazones with 5-hydroxy-1,4-naphthoquinone in an EtOAc/piperidine mixture, the reaction proceeded to give 5-hydroxy-2-(piperidin-1-yl)naphthalene-1,4-dione. The structures of the isolated products were proved by infrared, NMR (2D-NMR), mass spectra, and elemental analyses in addition to X-ray structure analysis. The reaction mechanisms are discussed. The anticancer screening of selected compounds showed broad-spectrum anticancer activity against most melanoma cancer cell lines, ovarian cancer OVCAR-3, central nervous system cancer SF-295 and U251, non-small cell lung cancer NCI-H23, renal cancer SN12C, and colon cancer HCT-15 and HCT-116. The selected compounds exhibited moderate to weak anticancer activity to other cell lines.

Correlation Between Structure and New Anti-cancer Activity of Some Antioxidants Following Chemical Structure Modification Does The Evidence Support This Correlation

“…Conclusions concerning their structure-activity connections based on the findings of biological tests include the following: (a) the presence of quinone ring in both 1C & 2C appears to boost anticancer activity; compared to that of other derivatives. Thus, other studies 15 support our findings and suggest that quinone-based heterocycles have broadspectrum anticancer activity. (b) Secondary amines were shown to be required for anticancer activity.…”

Synthesis and biological evaluation of coumarin-quinone hybrids as multifunctional bioactive agents

“…Natural quinones such as juglone and plumbagin exhibited growth inhibitory effects on microorganisms [14]. Benzoquinones play an important role in oxidative phosphorylation electron transfer processes and bioenergetic transport [15]. Quinones showed diverse pharmacological properties such as anti-inflammatory [16], antimicrobial [17] and anticancer [18][19][20].…”

Resistomycin Suppresses Prostate Cancer Cell Growth by Instigating Oxidative Stress, Mitochondrial Apoptosis, and Cell Cycle Arrest

“…Other quinone-related derivatives, such as 1-hydroxy-1-norresistomycin and resistoflavine, were found to have substantial cytotoxic activity in vitro against gastric adenocarcinoma (HMO2) and hepatic carcinoma (HepG2) cell lines, but their mechanisms of action require more study [20]. Furthermore, doxorubicin is a quinone medication that belongs to the anthracycline class, and it is used clinically to treat solid tumors and acute lymphoblastic and myeloblastic leukaemia [21]. Quinone's ability to bind covalently to DNA and microsomal proteins, as well as to enhance the production of reactive oxygen species, is what gives it its anticancer properties [21].…”

“…Furthermore, doxorubicin is a quinone medication that belongs to the anthracycline class, and it is used clinically to treat solid tumors and acute lymphoblastic and myeloblastic leukaemia [21]. Quinone's ability to bind covalently to DNA and microsomal proteins, as well as to enhance the production of reactive oxygen species, is what gives it its anticancer properties [21].…”