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Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis. 1-(3-Bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (10) and 3-benzoyl-1{[(phenylformamido)methanethioyl]amino}thiourea (12) gave a percentage viability of 17.9±5.6% and 11.2±0.9% against Trypanosoma brucei. Single crystal X-ray diffraction analysis of 1-benzoyl-3-(5-methyl-2-{[(phenylformamido)methanethioyl]amino}phenyl)thiourea (1), 3-benzoyl-1-(2-{[(phenylformamido)methanethioyl]amino}ethyl)thiourea (11), 3-benzoyl-1-{[(phenylformamido)methanethioyl]amino}thiourea (12) and 3-benzoyl-1-(4-{[(phenylformamido)methanethioyl]amino}butyl)thiourea (14) have been presented. 1-(3-Bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (10) gave a percentage inhibition of 97.03±0.37% against HIV-1 protease enzyme at a concentration of 100 µM.

Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis. 1-(3-Bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (10) and 3-benzoyl-1{[(phenylformamido)methanethioyl]amino}thiourea (12) gave a percentage viability of 17.9 ± 5.6% and 11.2 ± 0.9% against Trypanosoma brucei. Single crystal X-ray diffraction analysis of 1-benzoyl-3-(5-methyl-2-{[(phenylformamido)methanethioyl]amino}phenyl)thiourea (1), 3-benzoyl-1-(2-{[(phenylformamido)methanethioyl]amino}ethyl)thiourea (11), 3-benzoyl-1-{[(phenylformamido)methanethioyl]amino}thiourea (12) and 3-benzoyl-1-(4-{[(phenylformamido)methanethioyl]amino}butyl)thiourea (14) have been presented. 1-(3-Bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (10) gave a percentage inhibition of 97.03 ± 0.37% against HIV-1 protease enzyme at a concentration of 100 µM. [ABSTRACT FROM AUTHOR]

Currently, there is increasing interest in the potential of malaria inhibitors in Plasmodium falciparum activity. In this work, is propose a possible alternative to classifying 154 antimalarials, with P. falciparum activity. These antimalarials were synthesized by the Chibale's group (), with the goal of finding new insights on the binding pocket of the protein kinase PfPK5, PfPK7, PfCDPK1, PfCDPK4, PfMAP1, and PfPK6 of the malaria parasite. However, there is only information about crystallography of PfPK5 and PfPK7. The protein kinases PfCDPK1, PfCDPK4, PfMAP1, and PfPK6 were modeled using molecular homology. The validation used shows that our homology models can be an alternative for the protein kinases from P. falciparum, unknown today. The antimalarials were classified by taking into account the interactions in the hinge zone. These ligands bind to the kinase through the formation of one of two hydrogen bonds, with the backbone residues of the hinge region connecting the kinase N- and C-terminal loops. These interactions were supported by a reactivity chemistry analysis, using global chemical reactivity descriptors such as chemical potential, hardness, softness, electrophilicity, and the Fukui functions as local reactivity descriptors, within the Density Functional Theory (DFT) context. [ABSTRACT FROM AUTHOR]