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

Abstract

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.

Synthesis and in vitro antileishmanial efficacy of novel benzothiadiazine‐1,1‐dioxide derivatives

“…They are structurally related to the 1,1-dioxothiazine scaffold that is derived from a thiazine core. Besides the aforementioned therapeutic features, thiazine derivatives have also been found to have other biological properties, for example, the antiviral, [7] antimicrobial, [8] and antimalarial [9] properties of thiaplakortone A (Figure 1) and some of its derivatives. [10] Furthermore, benzothiadiazine-1,1-dioxide derivatives bearing other heterocyclic substituents have been synthesized in high yields; however, antileishmanial activity has yet to be reported.…”

3‐Bromoacetylcoumarin, a Crucial Key for Facial Synthesis of Biological Active Compounds

“…[77] thiazol-2H-chromen-2-one (59) and hydrazinyl-thiadiazin-2Hchromen-2-one (61) in excellent yields (Scheme 11). [78] Compound 59 exhibits moderate in vitro antimalarial activity with an IC 50 = 3.2 μM compared to the IC 50 of chloroquine against Plasmodium falciparum 3D7 (26 nM) and Dd2 (184 nM). [78] The suggested mechanism for the formation of compounds 59 and 61 involves nucleophilic addition of sulfur to 2, cyclization, elimination of water, another nucleophilic addition of the NH 2 group to the carbonyl, followed by another loss of water (Scheme 12).…”

“…Compound 59 exhibits moderate in vitro antimalarial activity with an IC 50 =3.2 μM compared to the IC 50 of chloroquine against Plasmodium falciparum 3D7 (26 nM) and Dd2 (184 nM) [78] …”

“…For the synthesis of three valuable pharmacophores (coumarins, pyrazoles and thiazoles) in one scaffold (79), Mahmoodi and Ghodsi [87] outlined a simple three-component, one-pot, cyclocondensation reaction of coumarin chalcone (78), thiosemicarbazide (58) and 3-bromoacetylcoumarin (2) (Scheme 21). This method gives good yields.…”

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

“…Four of these, 91a, 91b, 91c, and 91d, demonstrated modest efficacy against chloroquine-active and inactive P. falciparum strains, with half-maximal inhibitory concentration (IC 50 ) values of 3.2, 2.7, 2.7, and 2.8 and 3.2, 3.2, 3.1, and 3.5 µM, respectively. The structure-based study analysis indicated that the presence of chloro, bromo, and methoxy groups' substations on the thiazole ring was necessary to demonstrate the antimalarial activity [128]. A grading system was employed to select the sixty-six most potential PKG inhibitors.…”