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Leishmaniasis and cancer are two deadly diseases that plague the human population. There are a limited number of drugs available for the treatment of these diseases; however, their overuse has resulted in pathogenic resistance. Recent studies have indicated the repurposing of nitro‐containing compounds to be a new avenue into finding new treatments. In this study, new nitrofuranyl sulfonohydrazide derivatives were synthesized and evaluated for their in vitro antileishmanial and anticancer activities. The analogue 2h, featuring biphenyl moiety exhibited selective (SI > 10) submicromolar activity (IC50 0.97 μM) against acute promyelocytic leukemia cells hence was identified anticancer hit. This study revealed no antileishmanial hit. However, several promising analogues were uncovered and are worthy of further structural modifications to improve their toxicity and bioactivity profiles. [ABSTRACT FROM AUTHOR]

Over the past few years, great progress has been made in the development of high‐affinity adenosine A1 and/or A2A receptor antagonists—promising agents for the potential treatment of Parkinson's disease. Unfortunately, many of these compounds raise structure‐related concerns. The present study investigated the effect of ring closures on the rA1/A2A affinity of compounds containing a highly reactive α,β‐unsaturated carbonyl system, hence providing insight into the potential of heterocycles to address these concerns. A total of 12 heterocyclic compounds were synthesised and evaluated in silico and in vitro. The test compounds performed well upon qualitative assessment of drug‐likeness and were generally found to be free from potentially problematic fragments. Most also showed low/weak cytotoxicity. Results from radioligand binding experiments confirm that heterocycles (particularly 2‐substituted 3‐cyanopyridines) can replace the promiscuous α,β‐unsaturated ketone functional group without compromising A1/A2A affinity. Structure–activity relationships highlighted the importance of hydrogen bonds in binding to the receptors of interest. Compounds 3c (rA1Ki = 16 nM; rA2AKi = 65 nM) and 8a (rA1Ki = 102 nM; rA2AKi = 37 nM), which both act as A1 antagonists, showed significant dual A1/A2A affinity and may, therefore, inspire further investigation into heterocycles as potentially safe and potent adenosine receptor antagonists. [ABSTRACT FROM AUTHOR]

Currently available drugs being used to treat leishmaniasis have several shortcomings, including high toxicity, drug administration that requires hospitalization, and the emergence of parasite resistance against clinically used drugs. As a result, there is a dire need for the development of new antileishmanial drugs that are safe, affordable, and efficient. In this study, two new series of synthesized quinazolinone derivatives were investigated as potential future antileishmanial agents, by assessing their activities against the Leishmania (L.) donovani and L. major species. The cytotoxicity profiles of these derivatives were assessed in vitro on Vero cells. The compounds were found to be safer and without any toxic activities against mammalian cells, compared to the reference drug, halofuginone, a clinical derivative of febrifugine. However, they had demonstrated poor antileishmanial growth inhibition efficacies. The two compounds that had been found the most active were the mono quinazolinone 2d and the bisquinazolinone 5b with growth inhibitory efficacies of 35% and 29% for the L. major and L. donovani 9515 promastigotes, respectively. These outcomes had suggested structural redesign, inter alia the inclusion of polar groups on the quinazolinone ring, to potentially generate novel quinazolinone derivatives, endowed with effective antileishmanial potential. [ABSTRACT FROM AUTHOR]