Synthesis of thiazolyl hydrazonothiazolamines and 1,3,4‐thiadiazinyl hydrazonothiazolamines as a class of antimalarial agents

• Published in: Archiv der Pharmazie (Weinheim) 2019-12, Vol.352 (12), p.e1900079-n/a
• Main Authors: Sujatha, Kodam, Ommi, Naidu Babu, Mudiraj, Anwita, Babu, Phanithi Prakash, Vedula, Rajeswar Rao
• Format: Article
• Language: English
• Subjects: 2‐amino‐4‐methyl‐5‐acetylthiazole; Animals; antimalarial activity; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Antimalarials - toxicity; bithiazoles; Cell Line; Cell Survival - drug effects; Erythrocytes; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Hydrazones - toxicity; Inhibitory Concentration 50; Macrophages - drug effects; Malaria, Falciparum - drug therapy; Malaria, Falciparum - microbiology; Mice; Molecular Structure; multicomponent reactions; Plasmodium falciparum - drug effects; Structure-Activity Relationship; thiazolothiadiazines; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology; Triazoles - toxicity
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201900079

Novel thiazolyl hydrazonothiazolamines and 1,3,4‐thiadiazinyl hydrazonothiazolamines were synthesized by a facile one‐pot multicomponent approach by the reaction of 2‐amino‐4‐methyl‐5‐acetylthiazole, thiosemicarbazide or thiocarbohydrazide and phenacyl bromides or 3‐(2‐bromoacetyl)‐2H‐chromen‐2‐ones in acetic acid with good to excellent yields. These new compounds were screened in vitro for their antimalarial activity; among them, four compounds, 4h, 4i, 4k, 4l, showed moderate activity with half‐maximal inhibitory concentration (IC50) values of 3.2, 2.7, 2.7, and 2.8 and 3.2, 3.2, 3.1, and 3.5 μM against chloroquine‐sensitive and ‐resistant strains of Plasmodium falciparum, respectively. Compound 4l inhibited the ring stage growth of P. falciparum 3D7 at an IC90 concentration of 12.5 µM in a stage‐specific assay method, where the culture is incubated with specific stages of P. falciparum for 12 hr, and no activity was found against the trophozoite and schizont stages, confirming that 4l may have potent action against the ring stage of P. falciparum. Novel thiazolyl hydrazonothiazolamines and 1,3,4‐thiadiazinyl hydrazonothiazolamines were synthesized and screened for their in vitro antimalarial activity. Four compounds (4h, 4i, 4k, and 4l) showed moderate activity against chloroquine‐sensitive and resistant strains of Plasmodium falciparum. Compound 4l inhibited growth of the ring stage of P. falciparum 3D7.