Design, synthesis, and in vitro evaluation of thiosemicarbazone derivatives as anti-filarial agents.

Effective macrofilaricidal drugs are not commercially available, and in an endeavour to find out new macrofilaricidal agents, in this research work, thiosemicarbazone derivatives have been prepared and tested against adult Setaria digitata, a cattle filarial parasite, as a model nematode for the filarial parasite, Wuchereria bancrofti. Lipinski and Veber rules have been used to design these molecules and found out that all the designed molecules show drug-like molecular properties. The in vitro anti-filarial potential of thiosemicarbazones against S. digitata was carried out using worm motility and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction colorimetric assays at 100 µg/ml concentration for the incubation period of 24 h. The standard drugs used at present for filaria, Albendazole, Ivermectin and Diethylcarbamazine were not able to kill the adult filarial worms effectively. In contrast, phenyl thiosemicarbazones with trifluoromethyl substitution at 3rd and 4th positions, 2-pyrrolyl, and isatinyl made the adult worms immotile and also showed 69%-83% inhibition in formazan formation an indicator of non viability.

Pyridine appended 2-hydrazinylthiazole derivatives: design, synthesis, in vitro and in silico antimycobacterial studies.

An array of pyridine appended 2-hydrazinylthiazole derivatives has been synthesized to discover novel chemotherapeutic agents for Mycobacterium tuberculosis (Mtb). The drug-likeness of pyridine appended 2-hydrazinylthiazole derivatives was validated using the Lipinski and Veber rules. The designed thiazole molecules have been synthesized through Hantzsch thiazole methodologies. The in vitro antimycobacterial studies have been conducted using Luciferase reporter phage (LRP) assay. Out of thirty pyridine appended 2-hydrazinylthiazole derivatives, the compounds 2b, 3b, 5b, and 8b have exhibited good antimycobacterial activity against Mtb, an H37Rv strain with the minimum inhibitory concentration in the range of 6.40-7.14 µM. In addition, in vitro cytotoxicity of active molecules has been observed against Human Embryonic Kidney Cell lines (HEK293t) using MTT assay. The compounds 3b and 8b are nontoxic and their cell viability is 87% and 96.71% respectively. The in silico analyses of the pyridine appended 2-hydrazinylthiazole derivatives have been studied to find the mode of binding of the active compounds with KasA protein of Mtb. The active compounds showed a strong binding score (-5.27 to -6.23 kcal mol-1).

"Big Three" Infectious Diseases: Tuberculosis, Malaria and HIV/AIDS.

Infectious diseases have been evolving and re-evolving over the ages and causing immense misery to humans. Among them, some have been prevented and eradicated, but few are still threatening the modern era since their origin. The majority of these infectious diseases are poverty-driven, hence highly prevalent in the lower-income and mid-income countries of Africa and Asia. The world's deadliest infections, including Tuberculosis, Malaria and HIV/AIDS, have been considered as the "Big Three" infectious diseases (BTIDs). With leading infections and deaths every year, the BTIDs have been recognized as the world's greatest pandemics. In light of these alarming situations, this review has been aimed to provide a comprehensive overview of the current status of chemotherapeutics, associated challenges and future perspectives of BTIDs.

Thiosemicarbazone derivatives: Design, synthesis and in vitro antimalarial activity studies.

Different types of thiosemicarbazone derivatives were designed and tested for their Drug-Like Molecular (DLM) nature by using Lipinski and Veber rules. Subsequently, compounds with DLM properties were synthesized and characterized by spectral methods. In vitro antimalarial activity studies of the synthesized thiosemicarbazone derivatives have been carried out against Plasmodium falciparum, 3D7 strain using fluorescence assay method and found that the compounds, (E)-2-(1-(4-fluorophenyl)ethylidene)hydrazine-1-carbothioamide (6), (E)-2-(1-(3-bromophenyl) ethylidene) hydrazine-1-carbothioamide (15) and (E)-2-(3,4,5-trimethoxybenzylidene) hydrazine-1-carbothioamide (29) showed notable antimalarial activity with EC50 values of 13.54 µM, 15.83 µM and 14.52 µM respectively.