RSC Medicinal Chemistry Blog

A recent publication in MedChemComm from Doaa A. E. Issa et al.reports the synthesis and biological properties of a series of compounds containing the quinoxaline pharmacophore. Their choice of the quinoxaline motif was inspired by the antineoplastic and antimicrobial activity of other compounds containing this group.

Issa et al. synthesised a total of 15 compounds via a key hydrazino intermediate and evaluated 10 candidates at a single high dose for antitumour activity in the National Cancer Institute-60 cell screen. Compounds showing activity were further evaluated in a multi-dose assay. The team went on to assess the in vitro antibacterial activity and antifungal properties.

They found that several compounds in the series display antibacterial activity and one compound possesses both broad spectrum anticancer activity and antimicrobial activity against Pseudomonas aeruginosa.

Design, synthesis and biological evaluation of novel 1,2,4-triazolo and 1,2,4-triazino[4,3-a]quinoxalines as potential anticancer and antimicrobial agents
Doaa A. E. Issa, Nargues S. Habib and Abeer E. Abdel Wahab
Med. Chem. Commun., 2015, DOI: 10.1039/C4MD00257A

Decreased biosynthesis of hydrogen sulfide is found in a range of disease states. In cell based assays, hydrogen sulfide can prevent oxidant-induced cell damage. Together, these findings suggest that strategies to increase hydrogen sulfide bioavailability may have potential in the treatment of disease states such as hypertension and diabetes.

A recent article published in MedChemComm reports the synthesis of a hydrogen sulfide donor molecule coupled to a triphenylphosphonium cation (AP39).

The effects of this molecule on oxidative stress were compared against a compound with known vasodilatory activity in a cellular model. Lipophilic cation, such as the triphenylphosphonium cation, can accumulate within mitochondria (the main source of detrimental oxidant production within cells). The cytoprotective potency of the synthesised compound was greater than that of the comparator, suggesting that compounds capable of delivering hydrogen sulfide to mitochondria may have therapeutic potential.

The synthesis and functional evaluation of a mitochondria-targeted hydrogen sulfide donor, (10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)decyl)triphenylphosphonium bromide (AP39)
Sophie Le Trionnaire, Alexis Perry, Bartosz Szczesny, Csaba Szabo, Paul G. Winyard, Jacqueline L. Whatmore, Mark E. Wood and Matthew Whiteman
Med. Chem. Commun., 2014, DOI: 10.1039/C3MD00323J, Concise Article