Thiadiazoles: the appropriate pharmacological scaffolds with leishmanicidal and antimalarial activities: a review

Leishmaniasis and malaria are serious public health problems in tropical and sub-tropical regions worldwide. Development of drug-resistant strains has disrupted efforts to control the spread of these diseases in the world. The conventional antiparasitic chemotherapy still suffers from side effects and drug resistance. Therefore, the development of novel antimalarial and leishmanicidal drugs remains a critical topic to combat against these diseases. Five-membered heterocyclic systems have possessed antiparasitic activity such as thiadiazole scaffold which is a prevalent and an important heterocyclic ring. For this purpose, the authors introduce a series of synthetic thiadiazole derivatives with antileishamanial activity. Also, the authors searched a number of sources and articles to find thiadiazole derivatives with antileishamnial and antimalarial activity. Then all of the findings were reviewed. 5-nitroheteroaryl-1,3,4-Thiadiazole derivatives with different substituents at position 2  of the thiadiazole ring (8, 10-11) presented  the best antileishmanial activity with low toxicity compared with reference drug. Also, 1,3,4-thiadiazole-2-sulfonamide derivative (18) showed excellent inhibitory activity against pfCA as a special enzyme in Plasmodium falciparum. Thiadiazole scaffold has the suitable physicochemical and pharmacokinetic properties and still stays as a therapeutic target for the development of a novel lead in the medicinal chemistry. Therefore, the current review provides a brief summary of medicinal chemistry of thiadiazole ring and introduces novel leads possessing this nucleus with antimalarial and antileishmanial activities.v