Discovery of highly potent and selective antiparasitic new oxadiazole and hydroxy-oxindole small molecule hybrids

Fernandes, Fábio S.; Santos, Hugo; Lima, Samia R.; Conti, Caroline; Rodrigues, Manoel T.; Zeoly, Lucas A.; Ferreira, Leonardo L. G.; Krogh, Renata; Andricopulo, Adriano D.; Coelho, Fernando

doi:10.1016/j.ejmech.2020.112418

Cited by 10 publications

(7 citation statements)

References 58 publications

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“…Interestingly, some of the hybrid compounds exhibited excellent antiparasitic activity (IC 50 = 2.30 µM and 2.20 µM) and a low cytotoxic profile against human fibroblasts (CC 50 > 64 µM). Moreover, some of them also presented efficacy values similar or superior to benznidazole [ 96 ].…”

Section: Recent Development Of Indole-based Small Molecules Targeting Malaria Trypanosomiasis and Leishmaniasismentioning

confidence: 99%

Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis

Pacheco

Santos

2022

Molecules

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Human protozoan diseases represent a serious health problem worldwide, affecting mainly people in social and economic vulnerability. These diseases have attracted little investment in drug discovery, which is reflected in the limited available therapeutic arsenal. Authorized drugs present problems such as low efficacy in some stages of the disease or toxicity, which result in undesirable side effects and treatment abandonment. Moreover, the emergence of drug-resistant parasite strains makes necessary an even greater effort to develop safe and effective antiparasitic agents. Among the chemotypes investigated for parasitic diseases, the indole nucleus has emerged as a privileged molecular scaffold for the generation of new drug candidates. In this review, the authors provide an overview of the indole-based compounds developed against important parasitic diseases, namely malaria, trypanosomiasis and leishmaniasis, by focusing on the design, optimization and synthesis of the most relevant synthetic indole scaffolds recently reported.

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Section: Recent Development Of Indole-based Small Molecules Targeting Malaria Trypanosomiasis and Leishmaniasismentioning

confidence: 99%

Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis

Pacheco

Santos

2022

Molecules

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“…Heterocyclic compounds have been widely considered in drug design. As one of the most important heterocyclic compounds, 1,2,4-oxadiazole derivatives have exhibited a wide range of biological activities, including herbicidal [23,24], antibacterial [25,26], antifungal [27][28][29], insecticidal [30,31], and other biological activities [32][33][34][35]. Among them, tioxazafen, as the representative nematicide with a 1,2,4-oxdiazole as a core moiety, designed by Monsanto, acts as a new-type seed treatment agent for controlling nematodes [36].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments

Liu

Luo

Wang

et al. 2022

IJMS

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Plant diseases that are caused by fungi and nematodes have become increasingly serious in recent years. However, there are few pesticide chemicals that can be used for the joint control of fungi and nematodes on the market. To solve this problem, a series of novel 1,2,4-oxadiazole derivatives containing amide fragments were designed and synthesized. Additionally, the bioassays revealed that the compound F15 demonstrated excellent antifungal activity against Sclerotinia sclerotiorum (S. sclerotiorum) in vitro, and the EC50 value of that was 2.9 μg/mL, which is comparable with commonly used fungicides thifluzamide and fluopyram. Meanwhile, F15 demonstrated excellent curative and protective activity against S. sclerotiorum-infected cole in vivo. The scanning electron microscopy results showed that the hyphae of S. sclerotiorum treated with F15 became abnormally collapsed and shriveled, thereby inhibiting the growth of the hyphae. Furthermore, F15 exhibited favorable inhibition against the succinate dehydrogenase (SDH) of the S. sclerotiorum (IC50 = 12.5 μg/mL), and the combination mode and binding ability between compound F15 and SDH were confirmed by molecular docking. In addition, compound F11 showed excellent nematicidal activity against Meloidogyne incognita at 200 μg/mL, the corrected mortality rate was 93.2%, which is higher than that of tioxazafen.

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“…As an important heterocyclic compound, 1,2,4-oxadiazole has been widely studied by pesticide scientists with a wide range of biological activities, such as herbicidal (Hang, et al, 2014), antibacterial (Karad, et al, 2017), antifungal (Yang, et al, 2021), and insecticidal activities (Fernandes, et al, 2020), among others. Tioxazafen, which is one of the 1,2,4-oxadiazole compounds, was designed by Monsanto as a new type of seed treatment agent to control nematodes in soybean, corn, and cotton (Slomczynska, et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Activity of Novel Chalcone Derivatives Containing an 1,2,4-Oxadiazole Moiety

et al. 2022

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To discover a lead compound for agricultural use, 34 novel chalcone derivatives containing an 1,2,4-oxadiazole moiety were designed and synthesized. Their nematocidal activities against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus dipsaci and their antiviral activities against tobacco mosaic virus (TMV), pepper mild mottle virus (PMMoV), and tomato spotted wilt virus (TSWV) were evaluated. Biological assay results indicate that compounds A13 and A14 showed good nematocidal activities against B. xylophilus, A. besseyi, and D. dipsaci, with LC50 values of 35.5, 44.7, and 30.2 μg/ml and 31.8, 47.4, and 36.5 μg/ml, respectively, which are better than tioxazafen, fosthiazate, and abamectin. Furthermore, compound A16 demonstrated excellent protective activity against TMV, PMMoV, and TSWV, with EC50 values of 210.4, 156.2, and 178.2 μg/ml, respectively, which are superior to ningnanmycin (242.6, 218.4, and 180.5 μg/ml).

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Discovery of highly potent and selective antiparasitic new oxadiazole and hydroxy-oxindole small molecule hybrids

Cited by 10 publications

References 58 publications

Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis

Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis

Design, Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments

Design, Synthesis, and Biological Activity of Novel Chalcone Derivatives Containing an 1,2,4-Oxadiazole Moiety

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