Discovery of spirooxadiazoline oxindoles with dual-stage antimalarial activity

Lopes, Elizabeth A.; Mestre, Raquel; Fontinha, Diana; Legac, Jenny; Pei, Jinxin V.; Sanches-Vaz, Margarida; Mori, Mattia; Lehane, Adele M.; Rosenthal, Philip J.; Prudêncio, Miguel; Santos, Maria M. M.

doi:10.1016/j.ejmech.2022.114324

Cited by 13 publications

(9 citation statements)

References 44 publications

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“…Some of the synthesized spirooxindoles reveal promising properties against erythrocytic stage of P. falciparum and the liver-stage of P. berghei . This supports the possibility of developing active agents inhibiting both blood-stage and ( P. falciparum ) and liver-stage ( P. berghei ) parasites [ 65 ].…”

Section: Synthetic Spirooxindolessupporting

confidence: 60%

Spirooxindole: A Versatile Biologically Active Heterocyclic Scaffold

et al. 2023

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Spirooxindoles occupy an important place in heterocyclic chemistry. Many natural spirooxindole-containing compounds have been identified as bio-promising agents. Synthetic analogs have also been synthesized utilizing different pathways. The present article summarizes the recent development of both natural and synthetic spirooxindole-containing compounds prepared from isatin or its derivatives reported in the last five years. The spirooxindoles are categorized based on their mentioned biological properties.

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Section: Synthetic Spirooxindolessupporting

confidence: 60%

Spirooxindole: A Versatile Biologically Active Heterocyclic Scaffold

et al. 2023

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“…Despite several initiatives to reduce the incidence of protozoan disease, including treatment of giardiasis with the antibiotic metronidazole ( 13 ); treatment of malaria with artemisinin ( 14 ); and improvements in water, sanitation and hygiene conditions, protozoan infection remains a serious global health concern. Furthermore, drug resistance is a growing problem in veterinary medicine and may develop in humans; for example, metronidazole resistance has been reported in Endamoeba histolytica ( E. histolytica ) ( 15 ), Trichomonas vaginalis ( T. vaginalis ) ( 16 ) and G. lamblia ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

The roles of COX-2 in protozoan infection

2023

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Protozoan diseases cause great harm in animal husbandry and require human-provided medical treatment. Protozoan infection can induce changes in cyclooxygenase-2 (COX-2) expression. The role played by COX-2 in the response to protozoan infection is complex. COX-2 induces and regulates inflammation by promoting the synthesis of different prostaglandins (PGs), which exhibit a variety of biological activities and participate in pathophysiological processes in the body in a variety of ways. This review explains the roles played by COX-2 in protozoan infection and analyzes the effects of COX-2-related drugs in protozoan diseases.

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“…[13] Screening of large corporate libraries, such as the Tres Cantos Antimalarial Set (TCAMS) from GSK, [14] also identified novel indole-based antimalarials that were used as starting points for the development of the next generation antimalarial lead compounds, such as 3-piperidin-4-yl-indoles 2. [15] Many other indole-related antimalarial chemotypes, including indoloquinolines 3, [16] indolizinoindolones 4, [17,18] indole-containing pyrazino[2,1b]quinazoline-3,6-diones 5, [19] and spirooxadiazoline oxindoles 6 [20] have emerged from academic settings.…”

Section: Introductionmentioning

confidence: 99%

Facile Access to Structurally Diverse Antimalarial Indoles Using a One‐Pot A³ Coupling and Domino Cyclization Approach

et al. 2023

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A multistep and diversity‐oriented synthetic route aiming at the A3 coupling/domino cyclization of o‐ethynyl anilines, aldehydes and s‐amines is described. The preparation of the corresponding precursors included a series of transformations, such as haloperoxidation and Sonogashira cross‐coupling reactions, amine protection, desilylation and amine reduction. Some products of the multicomponent reaction underwent further detosylation and Suzuki coupling. The resulting library of structurally diverse compounds was evaluated against blood and liver stage malaria parasites, which revealed a promising lead with sub‐micromolar activity against intra‐erythrocytic forms of Plasmodium falciparum. The results from this hit‐to‐lead optimization are hereby reported for the first time.

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Discovery of spirooxadiazoline oxindoles with dual-stage antimalarial activity

Cited by 13 publications

References 44 publications

Spirooxindole: A Versatile Biologically Active Heterocyclic Scaffold

Spirooxindole: A Versatile Biologically Active Heterocyclic Scaffold

The roles of COX-2 in protozoan infection

Facile Access to Structurally Diverse Antimalarial Indoles Using a One‐Pot A³ Coupling and Domino Cyclization Approach

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Discovery of spirooxadiazoline oxindoles with dual-stage antimalarial activity

Cited by 13 publications

References 44 publications

Spirooxindole: A Versatile Biologically Active Heterocyclic Scaffold

Spirooxindole: A Versatile Biologically Active Heterocyclic Scaffold

The roles of COX-2 in protozoan infection

Facile Access to Structurally Diverse Antimalarial Indoles Using a One‐Pot A3 Coupling and Domino Cyclization Approach

Contact Info

Product

Resources

About

Facile Access to Structurally Diverse Antimalarial Indoles Using a One‐Pot A³ Coupling and Domino Cyclization Approach