Santos MC

References (3)

Title : Theoretical assessment of the performances of commercial oximes on the reactivation of acetylcholinesterase inhibited by the nerve agent A-242 (novichok) - Santos_2022_Food.Chem.Toxicol__113084
Author(s) : Santos MC , Botelho FD , Goncalves AS , Kuca K , Nepovimova E , Cavalcante SFA , Lima ALS , Franca TCC
Ref : Food & Chemical Toxicology , :113084 , 2022
Abstract : The nerve agents of the A-series are relatively recent chemical weapons with no antidote available yet. Once inside the human body, those chemicals act similarly to the classic nerve agents, by binding to the catalytic residue Serine 203 (Ser203) of human acetylcholinesterase (HssAChE) and thus preventing the proper function of this enzyme. However, there is no experimental evidence yet if the current antidotes for intoxication by nerve agents are also capable of restoring AChE inhibited by the nerve agents of the A-series. In order to launch some light on this issue, we used computational techniques (molecular docking, molecular dynamics and MM-PBSA interaction energy calculations) to assess the performances of the four currently available commercial oximes (2-PAM, HI-6, obidoxime and trimedoxime) when in contact with HssAChE inhibited by the agent A-242. Based on the near-attack conformation (NAC) criterion, our results suggest that the commercial oximes would have limited efficacy to reactivate the enzyme since they are not able to properly approach the adduct Ser203-A-242. Among those oximes, trimedoxime seems to be the most promising, since it showed lower values of energy in the MM-PBSA calculations, a higher stability inside the catalytic anionic center (CAS) of HssAChE, and was able to adopt a position closer to the NAC that could enable the reactivation mechanism.
ESTHER : Santos_2022_Food.Chem.Toxicol__113084
PubMedSearch : Santos_2022_Food.Chem.Toxicol__113084
PubMedID: 35489467

Title : Are the current commercially available oximes capable of reactivating acetylcholinesterase inhibited by the nerve agents of the A-series? - Santos_2022_Arch.Toxicol__
Author(s) : Santos MC , Botelho FD , Goncalves AS , Kitagawa DAS , Borges CVN , Carvalho-Silva T , Bernardo LB , Ferreira CN , Rodrigues RB , Ferreira Neto DC , Nepovimova E , Kuca K , LaPlante SR , Lima ALS , Franca TCC , Cavalcante SFA
Ref : Archives of Toxicology , : , 2022
Abstract : The misuse of novichok agents in assassination attempts has been reported in the international media since 2018. These relatively new class of neurotoxic agents is claimed to be more toxic than the agents of the G and V series and so far, there is no report yet in literature about potential antidotes against them. To shed some light into this issue, we report here the design and synthesis of NTMGMP, a surrogate of A-242 and also the first surrogate of a novichok agent useful for experimental evaluation of antidotes. Furthermore, the efficiency of the current commercial oximes to reactivate NTMGMP-inhibited acetylcholinesterase (AChE) was evaluated. The Ellman test was used to confirm the complete inhibition of AChE, and to compare the subsequent rates of reactivation in vitro as well as to evaluate aging. In parallel, molecular docking, molecular dynamics and MM-PBSA studies were performed on a computational model of the human AChE (HssAChE)/NTMGMP complex to assess the reactivation performances of the commercial oximes in silico. Experimental and theoretical studies matched the exact hierarchy of efficiency and pointed to trimedoxime as the most promising commercial oxime for reactivation of AChE inhibited by A-242.
ESTHER : Santos_2022_Arch.Toxicol__
PubMedSearch : Santos_2022_Arch.Toxicol__
PubMedID: 35666269

Title : Evolution of pathogenicity and sexual reproduction in eight Candida genomes - Butler_2009_Nature_459_657
Author(s) : Butler G , Rasmussen MD , Lin MF , Santos MA , Sakthikumar S , Munro CA , Rheinbay E , Grabherr M , Forche A , Reedy JL , Agrafioti I , Arnaud MB , Bates S , Brown AJ , Brunke S , Costanzo MC , Fitzpatrick DA , de Groot PW , Harris D , Hoyer LL , Hube B , Klis FM , Kodira C , Lennard N , Logue ME , Martin R , Neiman AM , Nikolaou E , Quail MA , Quinn J , Santos MC , Schmitzberger FF , Sherlock G , Shah P , Silverstein KA , Skrzypek MS , Soll D , Staggs R , Stansfield I , Stumpf MP , Sudbery PE , Srikantha T , Zeng Q , Berman J , Berriman M , Heitman J , Gow NA , Lorenz MC , Birren BW , Kellis M , Cuomo CA
Ref : Nature , 459 :657 , 2009
Abstract : Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
ESTHER : Butler_2009_Nature_459_657
PubMedSearch : Butler_2009_Nature_459_657
PubMedID: 19465905
Gene_locus related to this paper: canal-ATG15 , canal-bna7 , canal-c4yl13 , canal-LIP1 , canal-LIP2 , canal-LIP3 , canal-LIP4 , canal-LIP5 , canal-LIP6 , canal-LIP7 , canal-LIP8 , canal-LIP9 , canal-LIP10 , canal-ppme1 , canal-q5a0c9 , canal-q5a2i9 , canal-q5a042 , canal-q5ad17 , canal-q5aeu3 , canal-q5afp8 , canal-q5ag57 , canal-q5ai09 , canal-q5ai12 , canal-q5ajt3 , canal-q5akz5 , canal-q5apu4 , canal-q59l46 , canal-q59m48 , canal-q59nw6 , canal-q59u61 , canal-q59u64 , canal-q59vp0 , canal-q59y97 , canaw-c4ykb1 , canaw-c4yrn6 , canaw-c4yrn9 , canaw-c4yrr3 , canaw-c4yrv3 , canaw-c4ys26 , cantt-c5m3d7 , cantt-c5m3y5 , cantt-c5m4x0 , cantt-c5m5e8 , cantt-c5m5w2 , cantt-c5m8s7 , cantt-c5m9c2 , cantt-c5m465 , cantt-c5m751 , cantt-c5m793 , cantt-c5m893 , cantt-c5ma78 , cantt-c5mag0 , cantt-c5mbb8 , cantt-c5mc53 , cantt-c5md87 , cantt-c5mdy3 , cantt-c5mey7 , cantt-c5mfg0 , cantt-c5mfh8 , cantt-c5mg56 , cantt-c5mgj0 , cantt-c5mh75 , cantt-c5mh80 , cantt-c5mh89 , cantt-c5mhh0 , cantt-c5mhn5 , cantt-c5mij5 , cantt-c5min7 , clal4-c4xvt8 , clal4-c4xwy4 , clal4-c4xy03 , clal4-c4xyx9 , clal4-c4xzz1 , clal4-c4y3e1 , clal4-c4y4f2 , clal4-c4y4w8 , clal4-c4y5j4 , clal4-c4y5j9 , clal4-c4y7z7 , clal4-c4y8q1 , clal4-c4y035 , clal4-c4y481 , clal4-c4y538 , clal4-c4y898 , clal4-c4yas2 , clal4-c4yba6 , clal4-c4yba7 , clal4-c4yc85 , lodel-a5drz3 , lodel-a5ds97 , lodel-a5dsc0 , lodel-a5duu4 , lodel-a5duy7 , lodel-a5dv03 , lodel-a5dv46 , lodel-a5dw16 , lodel-a5dwv7 , lodel-a5dww6 , lodel-a5dxf3 , lodel-a5e0z5 , lodel-a5e1c1 , lodel-a5e1l4 , lodel-a5e1p3 , lodel-a5e2s1 , lodel-a5e2t8 , lodel-a5e2v2 , lodel-a5e4u8 , lodel-a5e5a9 , lodel-a5e5k1 , lodel-a5e5z7 , lodel-a5e6w1 , lodel-a5e028 , lodel-atg15 , lodel-kex1 , picgu-a5d9u2 , picgu-a5dav0 , picgu-a5dbk0 , picgu-a5dc45 , picgu-a5dc73 , picgu-a5dc74 , picgu-a5dc75 , picgu-a5ddt8 , picgu-a5dev7 , picgu-a5dh90 , picgu-a5dhe3 , picgu-a5di38 , picgu-a5dj06 , picgu-a5dkd8 , picgu-a5dle9 , picgu-a5dlj5 , picgu-a5dm19 , picgu-a5dn92 , picgu-a5dnr3 , picgu-a5dnt6 , picgu-a5dqu5 , picgu-a5dr14 , picgu-a5drl3 , picgu-atg15 , picgu-bna7 , picgu-a5d9q3 , picgu-a5dag9 , clal4-c4y5a2 , clal4-c4y0l0 , cantt-c5mcb1 , clal4-c4y8j2 , cantt-c5m494 , clals-a0a202gac7 , canal-hda1 , picgu-a5dks8 , lodel-a5drs6 , canpc-g8bbk1 , cantt-kex1 , clal4-kex1 , picgu-kex1