Molecular Docking, Toxicity and Antimicrobial Studies of P-Nitrobenzene
Sulphonamide Bearing Leucine --Isoleucine Dipeptide Carboxamides.
Abstract
Dipeptide carboxamide bearing nitrobenzene sulphonamides offers new
prospect towards the inhibition of hemoglobin degradation in
erythrocytes by Plasmodium falciparum; a malaria parasite and glycosyl
phosphatidyl inositol (GPI) pathway which controls the release of
variable surface glycoprotein (VSG) from Trypanosoma brucei. Structural
design carried out produced series of dipeptide carboxamide bearing
p-nitrobenzene sulphonamide compounds formed by coupling isoleucine
(Ileu) or leucine (Leu) bearing amine with p-nitrobenzene sulphonamide
bearing Ileu or Leu. Variation of coupling sequence between amidated
amino acids and p-nitrobenzene sulphonamide bearing amino acid generates
a library of 52 amidated Leu-Ileu dipeptide carboxamides bearing
p-nitrobenzene sulphonamide compounds. Antimicrobial properties were
evaluated using in-silico molecular docking. Protein residues E.coli
(coded: 5MMN), plasmepsin (coded: 3QSI), trypanosome brucei
dihydrofolate reductase pyrimethamine (coded: 3QFX) and prostaglandin
synthese (coded: 1EQG) were generated from protein data base and was
used to study biological activities of the compounds on bacterial,
malarial, trypanosomiasis and analgesic parasites respectively.
Ofloxacin, celecoxib, chloroquine and melarsoprol were used for docking
studies as reference drugs for antibacterial, analgesic, antimalarial
and antitrypanosomiasis respectively. Selected compounds from docking
studies were examined using ADMET to ascertain their toxicity profile.
Results of the antimicrobial properties reveal that some of the
compounds showed better binding affinity on plasmepsin and trypanosome
brucei parasites compared to standard drug used as reference in the
docking studies, making them a potential drug candidates for malaria and
trypanosomiasis treatment.