2‐Aroyl quinazolinone: Synthesis and in vitro anti‐parasitic activity

Setshedi, Koketso J; Beteck, Richard M.; Jesumoroti, Omobolanle J.; Ilbeigi, Kayhan; Mabille, Dorien; Caljon, Guy; Kooy, Frank van der; Legoabe, Lesetja J.

doi:10.1111/cbdd.14284

Cited by 5 publications

(4 citation statements)

References 38 publications

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“…Dose‐response curves were generated and EC 50 values calculated with GraphPad Prism, version 9.3 (San Diego, CA) using a sigmoidal four parameter logistic curve. Screening against T. brucei Squib 427, T. b. rhodesiense STIB‐90050, and T. cruzi was done using a previously reported protocol [52] …”

Section: Methodsmentioning

confidence: 99%

“…Screening against T. brucei Squib 427, T. b. rhodesiense STIB-90050, and T. cruzi was done using a previously reported protocol. [ 52 ]…”

Section: Methodsmentioning

confidence: 99%

“…Screening against T. brucei Squib 427, T. b. rhodesiense STIB-90050, and T. cruzi was done using a previously reported protocol. [52] 4.4. In vitro cytotoxicity evaluation HEK293 cells were cultured in DMEM supplemented with 10 % heat-inactivated FBS and 1 % penicillin-streptomycin.…”

Section: In Vitro Antitrypanosomal Assay Against T B Bruceimentioning

confidence: 99%

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Tractable Quinolone Hydrazides Exhibiting Sub‐Micromolar and Broad Spectrum Antitrypanosomal Activities

Chirwa,

Francisco,

Dube

et al. 2024

ChemMedChem

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Nagana and Human African Trypanosomiasis (HAT), caused by (sub)species of Trypanosoma, are diseases that impede human and animal health, and economic growth in Africa. The few drugs available have drawbacks including suboptimal efficacy, adverse effects, drug resistance, and difficult routes of administration. New drugs are needed. A series of 20 novel quinolone compounds with affordable synthetic routes was made and evaluated in vitro against Trypanosoma brucei and HEK293 cells. Of the 20 compounds, 12 had sub‐micromolar potencies against the parasite (EC50 values = 0.051‐0.57 µM), and most were non‐toxic to HEK293 cells (CC50 values >5 µM). Two of the most potent compounds presented sub‐micromolar activities against other trypanosome (sub)species (T. cruzi and T. b. rhodesiense). Although aqueous solubility is poor, both compounds possess good logD values (2‐3), and either robust or poor microsomal stability profiles. These varying attributes will be addressed in future reports.

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Section: Methodsmentioning

confidence: 99%

“…Screening against T. brucei Squib 427, T. b. rhodesiense STIB-90050, and T. cruzi was done using a previously reported protocol. [ 52 ]…”

Section: Methodsmentioning

confidence: 99%

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Tractable Quinolone Hydrazides Exhibiting Sub‐Micromolar and Broad Spectrum Antitrypanosomal Activities

Chirwa,

Francisco,

Dube

et al. 2024

ChemMedChem

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“…At present, only two drugs, benznidazole and nifurtimox, are available for the treatment of CD [23,24]. Both benznidazole and nifurtimox can result in diverse adverse side effects which sometimes result in abrupt treatment termination [25].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in vitro biological activity of chalcone derivatives as potential antiparasitic agents

Setshedi,

Beteck,

Ilbeigi

et al. 2024

Med Chem Res

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Kinetoplastids are a group of flagellated protozoans including medically important parasites of the genus Trypanosoma and Leishmania. The corresponding diseases have afflicted humans for centuries. In an effort to combat kinetoplastid infections, a set of 21 chalcones was synthesized and evaluated for their in vitro anti-protozoal efficacy against Trypanosoma brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania infantum. To ensure safety, these compounds underwent a selectivity evaluation by assessing toxicity against a human lung fibroblast cell line. Compound K4 exhibited remarkable and selective trypanocidal activity against T. b. brucei with IC50 value of 0.31 ± 0.27 µM and T. b. rhodesiense with IC50 value of 0.96 ± 0.86 µM. Compound K9 also showed significant trypanocidal activity against T. b. brucei (IC50: 0.45 ± 0.14 µM) and T. b. rhodesiense (IC50: 0.93 ± 0.51 µM). In both compounds, electron withdrawing groups are appended to the styrenyl moiety.

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Novel quinoline derivatives with broad‐spectrum antiprotozoal activities

Hartman,

Dube,

Legoabe

et al. 2024

Archiv der Pharmazie

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Several quinoline derivatives incorporating arylnitro and aminochalcone moieties were synthesized and evaluated in vitro against a broad panel of trypanosomatid protozoan parasites responsible for sleeping sickness (Trypanosoma brucei rhodesiense), nagana (Trypanosoma brucei brucei), Chagas disease (Trypanosoma cruzi), and leishmaniasis (Leishmania infantum). Several of the compounds demonstrated significant antiprotozoal activity. Specifically, compounds 2c, 2d, and 4i displayed submicromolar activity against T. b. rhodesiense with half‐maximal effective concentration (EC50) values of 0.68, 0.8, and 0.19 µM, respectively, and with a high selectivity relative to human lung fibroblasts and mouse primary macrophages (∼100‐fold). Compounds 2d and 4i also showed considerable activity against T. b. brucei with EC50 values of 1.4 and 0.4 µM, respectively.

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2‐Aroyl quinazolinone: Synthesis and in vitro anti‐parasitic activity

Cited by 5 publications

References 38 publications

Tractable Quinolone Hydrazides Exhibiting Sub‐Micromolar and Broad Spectrum Antitrypanosomal Activities

Tractable Quinolone Hydrazides Exhibiting Sub‐Micromolar and Broad Spectrum Antitrypanosomal Activities

Synthesis and in vitro biological activity of chalcone derivatives as potential antiparasitic agents

Novel quinoline derivatives with broad‐spectrum antiprotozoal activities

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