Matches in SemOpenAlex for { <https://semopenalex.org/work/W4311378002> ?p ?o ?g. }
- W4311378002 endingPage "1529" @default.
- W4311378002 startingPage "1529" @default.
- W4311378002 abstract "Malaria is an infectious disease widespread in underdeveloped tropical regions. The most severe form of infection is caused by Plasmodium falciparum, which can lead to development of cerebral malaria (CM) and is responsible for deaths and significant neurocognitive sequelae throughout life. In this context and considering the emergence and spread of drug-resistant P. falciparum isolates, the search for new antimalarial candidates becomes urgent. β-carbolines alkaloids are good candidates since a wide range of biological activity for these compounds has been reported. Herein, we designed 20 chemical entities and performed an in silico virtual screening against a pool of P. falciparum molecular targets, the Brazilian Malaria Molecular Targets (BRAMMT). Seven structures showed potential to interact with PfFNR, PfPK7, PfGrx1, and PfATP6, being synthesized and evaluated for in vitro antiplasmodial activity. Among them, compounds 3−6 and 10 inhibited the growth of the W2 strain at µM concentrations, with low cytotoxicity against the human cell line. In silico physicochemical and pharmacokinetic properties were found to be favorable for oral administration. The compound 10 provided the best results against CM, with important values of parasite growth inhibition on the 5th day post-infection for both curative (67.9%) and suppressive (82%) assays. Furthermore, this compound was able to elongate mice survival and protect them against the development of the experimental model of CM (>65%). Compound 10 also induced reduction of the NO level, possibly by interaction with iNOS. Therefore, this alkaloid showed promising activity for the treatment of malaria and was able to prevent the development of experimental cerebral malaria (ECM), probably by reducing NO synthesis." @default.
- W4311378002 created "2022-12-25" @default.
- W4311378002 creator A5002313263 @default.
- W4311378002 creator A5004186726 @default.
- W4311378002 creator A5011946768 @default.
- W4311378002 creator A5015128651 @default.
- W4311378002 creator A5032625673 @default.
- W4311378002 creator A5033089166 @default.
- W4311378002 creator A5036437117 @default.
- W4311378002 creator A5042298407 @default.
- W4311378002 creator A5045818259 @default.
- W4311378002 creator A5056464828 @default.
- W4311378002 creator A5060850002 @default.
- W4311378002 creator A5063296857 @default.
- W4311378002 creator A5074444499 @default.
- W4311378002 creator A5075226100 @default.
- W4311378002 creator A5080730364 @default.
- W4311378002 date "2022-12-13" @default.
- W4311378002 modified "2023-09-27" @default.
- W4311378002 title "Rational-Based Discovery of Novel β-Carboline Derivatives as Potential Antimalarials: From In Silico Identification of Novel Targets to Inhibition of Experimental Cerebral Malaria" @default.
- W4311378002 cites W1603332626 @default.
- W4311378002 cites W1966399595 @default.
- W4311378002 cites W1967606591 @default.
- W4311378002 cites W1968984252 @default.
- W4311378002 cites W1969503178 @default.
- W4311378002 cites W1969597610 @default.
- W4311378002 cites W1971456649 @default.
- W4311378002 cites W1982694126 @default.
- W4311378002 cites W1988952051 @default.
- W4311378002 cites W1992500853 @default.
- W4311378002 cites W1993238504 @default.
- W4311378002 cites W1995054863 @default.
- W4311378002 cites W1996511904 @default.
- W4311378002 cites W1997023449 @default.
- W4311378002 cites W1999216010 @default.
- W4311378002 cites W2005561713 @default.
- W4311378002 cites W2007381853 @default.
- W4311378002 cites W2011060686 @default.
- W4311378002 cites W2011805684 @default.
- W4311378002 cites W2014858249 @default.
- W4311378002 cites W2020251171 @default.
- W4311378002 cites W2021384011 @default.
- W4311378002 cites W2025195907 @default.
- W4311378002 cites W2027459042 @default.
- W4311378002 cites W2030215451 @default.
- W4311378002 cites W2045639174 @default.
- W4311378002 cites W2049153077 @default.
- W4311378002 cites W2057463574 @default.
- W4311378002 cites W2070760552 @default.
- W4311378002 cites W2083004221 @default.
- W4311378002 cites W2083004303 @default.
- W4311378002 cites W2086575000 @default.
- W4311378002 cites W2090826658 @default.
- W4311378002 cites W2101937547 @default.
- W4311378002 cites W2109863545 @default.
- W4311378002 cites W2111968186 @default.
- W4311378002 cites W2114918609 @default.
- W4311378002 cites W2118493661 @default.
- W4311378002 cites W2130025072 @default.
- W4311378002 cites W2131163323 @default.
- W4311378002 cites W2134967712 @default.
- W4311378002 cites W2135732933 @default.
- W4311378002 cites W2135874703 @default.
- W4311378002 cites W2136200837 @default.
- W4311378002 cites W2143634481 @default.
- W4311378002 cites W2144877918 @default.
- W4311378002 cites W2148446039 @default.
- W4311378002 cites W2152262846 @default.
- W4311378002 cites W2160384674 @default.
- W4311378002 cites W2171480404 @default.
- W4311378002 cites W2198907191 @default.
- W4311378002 cites W2409898799 @default.
- W4311378002 cites W2523145084 @default.
- W4311378002 cites W2570602609 @default.
- W4311378002 cites W2593436234 @default.
- W4311378002 cites W2609751086 @default.
- W4311378002 cites W2767314890 @default.
- W4311378002 cites W2782661480 @default.
- W4311378002 cites W2785594347 @default.
- W4311378002 cites W2886532357 @default.
- W4311378002 cites W2915821630 @default.
- W4311378002 cites W2936074388 @default.
- W4311378002 cites W2983813868 @default.
- W4311378002 cites W3021114071 @default.
- W4311378002 cites W3021378057 @default.
- W4311378002 cites W3041119915 @default.
- W4311378002 cites W3044178692 @default.
- W4311378002 cites W3048917826 @default.
- W4311378002 cites W3081996192 @default.
- W4311378002 cites W3083129537 @default.
- W4311378002 cites W3084158514 @default.
- W4311378002 cites W3091892253 @default.
- W4311378002 cites W3118339635 @default.
- W4311378002 cites W4200561470 @default.
- W4311378002 cites W4211051628 @default.
- W4311378002 cites W4220969293 @default.
- W4311378002 cites W4221009689 @default.
- W4311378002 cites W4225134021 @default.