المؤلفون: Wilson Lim (5147105), Bertrand Nyuykonge (9853203), Kimberly Eadie (475170), Mickey Konings (5147117), Juli Smeets (12047403), Ahmed Fahal (386197), Alexandro Bonifaz (619531), Matthew Todd (6500537), Benjamin Perry (5184542), Kirandeep Samby (10686802), Jeremy Burrows (811255), Annelies Verbon (175842), Wendy van de Sande (701616)

مصطلحات موضوعية: Biochemistry, Microbiology, Pharmacology, Ecology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, pandemic response box, minimal inhibitory concentrations, medicinal chemistry optimisation, fungal orders sordariales, aminoquinolone derivative tafenoquine, madurella tropicana <, madurella pseudomycetomatis <, galleria mellonella <, find novel drugs, falciformispora senegalensis <, div >< p, seven inhibited growth, promising drug candidates, madurella mycetomatis <, benzimidazole carbamates fenbendazole, eumycetoma , promising candidates, mycetomatis <, vivo <, vitro <, novel antifungals, treat eumycetoma, significantly prolong, mycetos )

الوصف: Madurella pseudomycetomatis , Madurella mycetomatis and Madurella tropicana belong to the order Sordariales, while Medicopsis romeroi and Falciformispora senegalensis belong to the order Pleosporales. Bolded characters indicate the fungal species used in this evaluation.

العلاقة: https://figshare.com/articles/figure/Phylogenetic_tree_of_the_most_common_eumycetoma_causing_agents_/19124715Test

الإتاحة: https://doi.org/10.1371/journal.pntd.0010159.g001Test

المؤلفون: Wilson Lim (5147105), Bertrand Nyuykonge (9853203), Kimberly Eadie (475170), Mickey Konings (5147117), Juli Smeets (12047403), Ahmed Fahal (386197), Alexandro Bonifaz (619531), Matthew Todd (6500537), Benjamin Perry (5184542), Kirandeep Samby (10686802), Jeremy Burrows (811255), Annelies Verbon (175842), Wendy van de Sande (701616)

مصطلحات موضوعية: Biochemistry, Microbiology, Pharmacology, Ecology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, pandemic response box, minimal inhibitory concentrations, medicinal chemistry optimisation, fungal orders sordariales, aminoquinolone derivative tafenoquine, madurella tropicana <, madurella pseudomycetomatis <, galleria mellonella <, find novel drugs, falciformispora senegalensis <, div >< p, seven inhibited growth, promising drug candidates, madurella mycetomatis <, benzimidazole carbamates fenbendazole, eumycetoma , promising candidates, mycetomatis <, vivo <, vitro <, novel antifungals, treat eumycetoma, significantly prolong, mycetos )

الوصف: (XLSX)

العلاقة: https://figshare.com/articles/dataset/All_information_and_data_of_the_400_compounds_tested_from_the_Pandemic_Response_Box_/19124709Test

الإتاحة: https://doi.org/10.1371/journal.pntd.0010159.s001Test

المؤلفون: Wilson Lim (5147105), Bertrand Nyuykonge (9853203), Kimberly Eadie (475170), Mickey Konings (5147117), Juli Smeets (12047403), Ahmed Fahal (386197), Alexandro Bonifaz (619531), Matthew Todd (6500537), Benjamin Perry (5184542), Kirandeep Samby (10686802), Jeremy Burrows (811255), Annelies Verbon (175842), Wendy van de Sande (701616)

مصطلحات موضوعية: Biochemistry, Microbiology, Pharmacology, Ecology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, pandemic response box, minimal inhibitory concentrations, medicinal chemistry optimisation, fungal orders sordariales, aminoquinolone derivative tafenoquine, madurella tropicana <, madurella pseudomycetomatis <, galleria mellonella <, find novel drugs, falciformispora senegalensis <, div >< p, seven inhibited growth, promising drug candidates, madurella mycetomatis <, benzimidazole carbamates fenbendazole, eumycetoma , promising candidates, mycetomatis <, vivo <, vitro <, novel antifungals, treat eumycetoma, significantly prolong, mycetos )

الوصف: Panel A divides the compounds into their respective groups as indicated in the Pandemic Response Box. Most compounds exhibiting potency at 25 μM falls under the antifungals and antibacterial. Less than 21% are antivirals. No antivirals inhibit M . romeroi growth at 25 μM. Panel B displays a Venn diagram. Four compounds–Fenbendazole, Carbendazim, Tafenoquine and MMV1578570 were able to inhibit all 5 fungal species tested here.

العلاقة: https://figshare.com/articles/figure/Pandemic_response_box_compounds_exhibiting_potency_at_25_M_against_the_tested_fungal_species_/19124721Test

الإتاحة: https://doi.org/10.1371/journal.pntd.0010159.g003Test

المؤلفون: Wilson Lim (5147105), Bertrand Nyuykonge (9853203), Kimberly Eadie (475170), Mickey Konings (5147117), Juli Smeets (12047403), Ahmed Fahal (386197), Alexandro Bonifaz (619531), Matthew Todd (6500537), Benjamin Perry (5184542), Kirandeep Samby (10686802), Jeremy Burrows (811255), Annelies Verbon (175842), Wendy van de Sande (701616)

مصطلحات موضوعية: Biochemistry, Microbiology, Pharmacology, Ecology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, pandemic response box, minimal inhibitory concentrations, medicinal chemistry optimisation, fungal orders sordariales, aminoquinolone derivative tafenoquine, madurella tropicana <, madurella pseudomycetomatis <, galleria mellonella <, find novel drugs, falciformispora senegalensis <, div >< p, seven inhibited growth, promising drug candidates, madurella mycetomatis <, benzimidazole carbamates fenbendazole, eumycetoma , promising candidates, mycetomatis <, vivo <, vitro <, novel antifungals, treat eumycetoma, significantly prolong, mycetos )

الوصف: Only three benzimidazole carbamates, MMV1782387, MMV0031343 (fenbendazole) and MMV344625 (carbendazim) were tested in vivo , while the rest wasn’t able to inhibit M . mycetomatis growth at 25μM. Due to MMY1782387 and fenbendazole’s efficacy in vivo , benzimidazole carbamates are a promising group of compounds to investigate as part of the MycetOS initiative in search for novel drugs to treat eumycetoma.

العلاقة: https://figshare.com/articles/figure/The_8_benzimidazole_carbamates_from_the_Pathogen_Box_Stasis_Box_and_Pandemic_Response_Box_tested_for_i_M_i_i_mycetomatis_i_/19124727Test

الإتاحة: https://doi.org/10.1371/journal.pntd.0010159.g005Test

المؤلفون: Wilson Lim (5147105), Bertrand Nyuykonge (9853203), Kimberly Eadie (475170), Mickey Konings (5147117), Juli Smeets (12047403), Ahmed Fahal (386197), Alexandro Bonifaz (619531), Matthew Todd (6500537), Benjamin Perry (5184542), Kirandeep Samby (10686802), Jeremy Burrows (811255), Annelies Verbon (175842), Wendy van de Sande (701616)

مصطلحات موضوعية: Biochemistry, Microbiology, Pharmacology, Ecology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, pandemic response box, minimal inhibitory concentrations, medicinal chemistry optimisation, fungal orders sordariales, aminoquinolone derivative tafenoquine, madurella tropicana <, madurella pseudomycetomatis <, galleria mellonella <, find novel drugs, falciformispora senegalensis <, div >< p, seven inhibited growth, promising drug candidates, madurella mycetomatis <, benzimidazole carbamates fenbendazole, eumycetoma , promising candidates, mycetomatis <, vivo <, vitro <, novel antifungals, treat eumycetoma, significantly prolong, mycetos )

الوصف: Panel A, Madurella mycetomatis ; B, Madurella tropicana ; C, Madurella tropicana ; D, Falciformispora senegalensis ; and E, Medicopsis romeroi . 47, 42, 37, 26 and 7 compounds were able to inhibit the tested fungal isolates respectively. The horizontal black-lines in the figures shows the growth percentage at 20%. Compounds situated under the black-lines were able that inhibited more than 80% fungal growth and thus a growth below 20%.

العلاقة: https://figshare.com/articles/figure/Compounds_inhibiting_growth_of_the_Sordariomycetes_and_the_Pleosporaleans_at_25_M_/19124718Test

الإتاحة: https://doi.org/10.1371/journal.pntd.0010159.g002Test

المؤلفون: Wilson Lim (5147105), Bertrand Nyuykonge (9853203), Kimberly Eadie (475170), Mickey Konings (5147117), Juli Smeets (12047403), Ahmed Fahal (386197), Alexandro Bonifaz (619531), Matthew Todd (6500537), Benjamin Perry (5184542), Kirandeep Samby (10686802), Jeremy Burrows (811255), Annelies Verbon (175842), Wendy van de Sande (701616)

مصطلحات موضوعية: Biochemistry, Microbiology, Pharmacology, Ecology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, pandemic response box, minimal inhibitory concentrations, medicinal chemistry optimisation, fungal orders sordariales, aminoquinolone derivative tafenoquine, madurella tropicana <, madurella pseudomycetomatis <, galleria mellonella <, find novel drugs, falciformispora senegalensis <, div >< p, seven inhibited growth, promising drug candidates, madurella mycetomatis <, benzimidazole carbamates fenbendazole, eumycetoma , promising candidates, mycetomatis <, vivo <, vitro <, novel antifungals, treat eumycetoma, significantly prolong, mycetos )

الوصف: The blue dashed line in all panels represents the non-infected controls while the black line represents the infected control. Panel A displays the survival of larvae treated with azoles Miconazole, Ravuconazole, Oteseconazole, Eberconazole and Luliconazole. Panel B, the survival of larvae treated with benzimidazole carbamates Fenbendazole, Carbendazim and MMV1782387. Panel C and D displays the survival of larvae treated with the other MMV compounds MMV1634491, MMV019724, Alexidine, Amorolfine, Tafenoquine and Olorofim. Significant survival was displayed as * (0.01

العلاقة: https://figshare.com/articles/figure/Survival_curves_of_i_Galleria_mellonella_i_larvae_infected_with_i_Madurella_mycetomatis_i_and_treated_with_selected_compounds_/19124724Test

الإتاحة: https://doi.org/10.1371/journal.pntd.0010159.g004Test

المؤلفون: Wilson Lim (5147105), Bertrand Nyuykonge (9853203), Kimberly Eadie (475170), Mickey Konings (5147117), Juli Smeets (12047403), Ahmed Fahal (386197), Alexandro Bonifaz (619531), Matthew Todd (6500537), Benjamin Perry (5184542), Kirandeep Samby (10686802), Jeremy Burrows (811255), Annelies Verbon (175842), Wendy van de Sande (701616)

مصطلحات موضوعية: Biochemistry, Microbiology, Pharmacology, Ecology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, pandemic response box, minimal inhibitory concentrations, medicinal chemistry optimisation, fungal orders sordariales, aminoquinolone derivative tafenoquine, madurella tropicana <, madurella pseudomycetomatis <, galleria mellonella <, find novel drugs, falciformispora senegalensis <, div >< p, seven inhibited growth, promising drug candidates, madurella mycetomatis <, benzimidazole carbamates fenbendazole, eumycetoma , promising candidates, mycetomatis <, vivo <, vitro <, novel antifungals, treat eumycetoma, significantly prolong, mycetos )

الوصف: Percentage growth of M . mycetomatis at 100 μM and 25 μM, IC50 and MIC50 values, Galleria mellonella larvae survival and in vivo significance of the eight benzimidazole carbamates from the Pathogen Box, Stasis Box and Pandemic Response Box tested against Madurella mycetomatis .

العلاقة: https://figshare.com/articles/dataset/Percentage_growth_of_i_M_i_i_mycetomatis_i_at_100_M_and_25_M_IC50_and_MIC50_values_i_Galleria_mellonella_i_larvae_survival_and_i_in_vivo_i_significance_of_the_eight_benzimidazole_carbamates_from_the_Pathogen_Box_Stasis_Box_and_Pandemic_Resp/19124742Test

الإتاحة: https://doi.org/10.1371/journal.pntd.0010159.t003Test

المؤلفون: Wilson Lim (5147105), Bertrand Nyuykonge (9853203), Kimberly Eadie (475170), Mickey Konings (5147117), Juli Smeets (12047403), Ahmed Fahal (386197), Alexandro Bonifaz (619531), Matthew Todd (6500537), Benjamin Perry (5184542), Kirandeep Samby (10686802), Jeremy Burrows (811255), Annelies Verbon (175842), Wendy van de Sande (701616)

مصطلحات موضوعية: Biochemistry, Microbiology, Pharmacology, Ecology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, pandemic response box, minimal inhibitory concentrations, medicinal chemistry optimisation, fungal orders sordariales, aminoquinolone derivative tafenoquine, madurella tropicana <, madurella pseudomycetomatis <, galleria mellonella <, find novel drugs, falciformispora senegalensis <, div >< p, seven inhibited growth, promising drug candidates, madurella mycetomatis <, benzimidazole carbamates fenbendazole, eumycetoma , promising candidates, mycetomatis <, vivo <, vitro <, novel antifungals, treat eumycetoma, significantly prolong, mycetos )

الوصف: Compounds with MIC50 value indicated with an asterisk (*) were determined in previous works [ 19 – 21 ]. Their efficacy to M . mycetomatis is again demonstrated here with their low IC50 values.

العلاقة: https://figshare.com/articles/dataset/Class_mode_of_action_IC50_and_MIC50_values_of_the_20_most_potent_compounds_in_the_Pandemic_Response_Box_against_i_Madurella_mycetomatis_i_/19124739Test

الإتاحة: https://doi.org/10.1371/journal.pntd.0010159.t002Test

المؤلفون: Wilson Lim (5147105), Bertrand Nyuykonge (9853203), Kimberly Eadie (475170), Mickey Konings (5147117), Juli Smeets (12047403), Ahmed Fahal (386197), Alexandro Bonifaz (619531), Matthew Todd (6500537), Benjamin Perry (5184542), Kirandeep Samby (10686802), Jeremy Burrows (811255), Annelies Verbon (175842), Wendy van de Sande (701616)

مصطلحات موضوعية: Biochemistry, Microbiology, Pharmacology, Ecology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, pandemic response box, minimal inhibitory concentrations, medicinal chemistry optimisation, fungal orders sordariales, aminoquinolone derivative tafenoquine, madurella tropicana <, madurella pseudomycetomatis <, galleria mellonella <, find novel drugs, falciformispora senegalensis <, div >< p, seven inhibited growth, promising drug candidates, madurella mycetomatis <, benzimidazole carbamates fenbendazole, eumycetoma , promising candidates, mycetomatis <, vivo <, vitro <, novel antifungals, treat eumycetoma, significantly prolong, mycetos )

الوصف: Compounds from the Pandemic Response Box that inhibits the Sordariomycetes and the Pleosporaleans under 25 μM.

العلاقة: https://figshare.com/articles/dataset/Compounds_from_the_Pandemic_Response_Box_that_inhibits_the_Sordariomycetes_and_the_Pleosporaleans_under_25_M_/19124733Test

الإتاحة: https://doi.org/10.1371/journal.pntd.0010159.t001Test

المؤلفون: Waring, Michael J., Leach, Andrew G., Miller, Duncan C.

المصدر: Waring , M J , Leach , A G & Miller , D C 2015 , Challenges in the Medicinal Chemical Optimization of Binding Kinetics . in Thermodynamics and Kinetics of Drug Binding . John Wiley & Sons Ltd , pp. 191-210 . https://doi.org/10.1002/9783527673025.ch10Test

مصطلحات موضوعية: Binding kinetics, Medicinal chemistry optimisation, Residence time, Structure-kinetic relationships

الوصف: This chapter describes the key considerations and challenges to optimizing binding kinetics. The challenges relate both to our ability to measure on and off rates in a manner that informs optimization but also in our limited molecular understanding of the processes that govern on and off rates. The effects of individual molecular interactions and bulk physicochemical properties are discussed. A number of significant case studies from the literature are described, which serve to highlight these principles. These examples also illustrate that empirical optimization of residence time is possible if given adequate attention during optimization and that some of the principles discussed may have general applicability.

الإتاحة: https://doi.org/10.1002/9783527673025.ch10Test
https://research.manchester.ac.uk/en/publications/1799a53e-ad2a-4b8b-8fb8-b60005352d91Test
http://www.scopus.com/inward/record.url?scp=84979719172&partnerID=8YFLogxKTest