Recent research progress on small molecule compounds and its derivatives of antiparasitic drugs

Wang, Ting; Wang, Lin; He, Jiang; Li, Chang; Shi, Jianyou

doi:10.1016/j.cclet.2023.108359

Cited by 2 publications

(3 citation statements)

References 142 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alkaloids also inhibit the work of the topoisomerase enzyme, which participates in the various vital activities of the parasite, including the process of DNA replication and thus stopping the physiological activities and the parasite's destruction [21], [22]. In addition to inhibiting the activity of Acetylcholinesterase enzyme (AchE), which prevents the passage of ions through the cell membrane and affects the vital activities of the parasite, thus causing cell breakdown and parasite death [23], [24].…”

Section: Resultsmentioning

confidence: 99%

Effect of Alcoholic Extract of Carrichtera annua Plant on the Growth of Leishmania donovani Parasite, In vitro Study

Shahatha,

AlFahdawy,

Dhulkefl

et al. 2024

IOP Conf. Ser.: Earth Environ. Sci.

View full text Add to dashboard Cite

The current study was conducted to find out the efficacy of the alcohol extract of Al-Khashin plant Carrichtera annua plant in treating the Leishmania donovani parasite In vitro, where the concentration of 1.5 mg/ml resulted in an inhibitory effect on the growth of the promastigote of parasites at a percentage of 50% (LCD50) during 96 an hour at a rate of 38.1 x 103 cells/cm3 compared to the control treatment 76.2 x 103 cells/cm3, the results showed the significant inhibitory effect of the alcohol extract of Al-Khashin plant on the growth of Leishmania parasites, which led to a decrease in the number of generations and an increase in their time, as the number of generations reached 108.7 generation compared to the control treatment reached 232.5 generations using the same concentration within 96 hours of treatment, an inverse relationship was observed between increased concentration and generation time. The conclusion of the present study is the high efficiency of C. annua alcoholic extract in treating the L. donovani parasites as it led to an apparent inhibition of the growth of promastigote that was treated with different concentrations of the alcoholic extract of the plant.

show abstract

Section: Resultsmentioning

confidence: 99%

Effect of Alcoholic Extract of Carrichtera annua Plant on the Growth of Leishmania donovani Parasite, In vitro Study

Shahatha,

AlFahdawy,

Dhulkefl

et al. 2024

IOP Conf. Ser.: Earth Environ. Sci.

View full text Add to dashboard Cite

show abstract

“…Only two drugs, benznidazole and nifurtimox, are currently approved for the treatment of Chagas disease [3,[7][8][9]. These therapeutics are effective in treating the infections; however, they lead to adverse reactions and poor patient compliance [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…cruzi hexokinase (TcHxK) and glucokinase (TcGlcK) are ATP-dependent glycolytic enzymes involved in energy metabolism of the parasite [15,16]. Their key role is in the production of D-glucose-6-phosphate (G6P), which is a metabolite positioned between glycolysis, gluconeogenesis, and the pentose phosphate pathway (PPP) [7,17,18]. Two life stages are commonly observed during human infection: the trypomastigote and the intracellular amastigote [5].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Strong 3-Nitro-2-Phenyl-2H-Chromene Analogues as Antitrypanosomal Agents and Inhibitors of Trypanosoma cruzi Glucokinase

Carey,

O’Neill,

Conner

et al. 2024

IJMS

View full text Add to dashboard Cite

Chagas disease is one of the world’s neglected tropical diseases, caused by the human pathogenic protozoan parasite Trypanosoma cruzi. There is currently a lack of effective and tolerable clinically available therapeutics to treat this life-threatening illness and the discovery of modern alternative options is an urgent matter. T. cruzi glucokinase (TcGlcK) is a potential drug target because its product, d-glucose-6-phosphate, serves as a key metabolite in the pentose phosphate pathway, glycolysis, and gluconeogenesis. In 2019, we identified a novel cluster of TcGlcK inhibitors that also exhibited anti-T. cruzi efficacy called the 3-nitro-2-phenyl-2H-chromene analogues. This was achieved by performing a target-based high-throughput screening (HTS) campaign of 13,040 compounds. The selection criteria were based on first determining which compounds strongly inhibited TcGlcK in a primary screen, followed by establishing on-target confirmed hits from a confirmatory assay. Compounds that exhibited notable in vitro trypanocidal activity over the T. cruzi infective form (trypomastigotes and intracellular amastigotes) co-cultured in NIH-3T3 mammalian host cells, as well as having revealed low NIH-3T3 cytotoxicity, were further considered. Compounds GLK2-003 and GLK2-004 were determined to inhibit TcGlcK quite well with IC50 values of 6.1 µM and 4.8 µM, respectively. Illuminated by these findings, we herein screened a small compound library consisting of thirteen commercially available 3-nitro-2-phenyl-2H-chromene analogues, two of which were GLK2-003 and GLK2-004 (compounds 1 and 9, respectively). Twelve of these compounds had a one-point change from the chemical structure of GLK2-003. The analogues were run through a similar primary screening and confirmatory assay protocol to our previous HTS campaign. Subsequently, three in vitro biological assays were performed where compounds were screened against (a) T. cruzi (Tulahuen strain) infective form co-cultured within NIH-3T3 cells, (b) T. brucei brucei (427 strain) bloodstream form, and (c) NIH-3T3 host cells alone. We report on the TcGlcK inhibitor constant determinations, mode of enzyme inhibition, in vitro antitrypanosomal IC50 determinations, and an assessment of structure–activity relationships. Our results reveal that the 3-nitro-2-phenyl-2H-chromene scaffold holds promise and can be further optimized for both Chagas disease and human African trypanosomiasis early-stage drug discovery research.

show abstract

Recent research progress on small molecule compounds and its derivatives of antiparasitic drugs

Cited by 2 publications

References 142 publications

Effect of Alcoholic Extract of Carrichtera annua Plant on the Growth of Leishmania donovani Parasite, In vitro Study

Effect of Alcoholic Extract of Carrichtera annua Plant on the Growth of Leishmania donovani Parasite, In vitro Study

Discovery of Strong 3-Nitro-2-Phenyl-2H-Chromene Analogues as Antitrypanosomal Agents and Inhibitors of Trypanosoma cruzi Glucokinase

Contact Info

Product

Resources

About