thiolactomycin and Malaria--Falciparum

thiolactomycin has been researched along with Malaria--Falciparum* in 2 studies

Other Studies

2 other study(ies) available for thiolactomycin and Malaria--Falciparum

Article	Year
CoMFA, CoMSIA, and docking studies on thiolactone-class of potent anti-malarials: identification of essential structural features modulating anti-malarial activity. Chemical biology & drug design, 2011, Volume: 78, Issue:3 The integrated ligand- and structure-based drug design techniques have been applied on a homogeneous dataset of thiolactone-class of potent anti-malarials, to explore the essential structural features for the inhibition of Plasmodium falciparum. Developed CoMFA (q(2) = 0.716) and CoMSIA (q(2) = 0.632) models well explained structure-activity variation in both the training (CoMFA R(2) = 0.948 & CoMSIA R(2) = 0.849) and test set (CoMFA R(2) (pred) = 0.789 & CoMSIA R(2) (pred) = 0.733) compounds. The docking and scoring of the most active compound 10 into the active site of high-resolution (2.35 Å) structure of FabB-TLM binary complex (PDB-ID: 1FJ4) indicated that thiolactone core of this compound forms bifurcated H-bonding with two catalytic residues His298 and His333, and its saturated decyl side group is stabilized by hydrophobic interactions with the residues of a small hydrophobic groove, illustrating that the active site architecture, including two catalytic histidines and a small hydrophobic groove, is vital for protein-ligand interaction. In particular, the length and flexibility of the side group attached to the position 5 of thiolactone have been observed to play a significant role in the interaction with FabB enzyme. These results present scope for rational design of thiolactone-class of compounds that could furnish improved anti-malarial activity. Topics: Antimalarials; Drug Design; Humans; Malaria, Falciparum; Models, Molecular; Plasmodium falciparum; Quantitative Structure-Activity Relationship; Thiophenes	2011
Comparison of the antiplasmodial and falcipain-2 inhibitory activity of beta-amino alcohol thiolactone-chalcone and isatin-chalcone hybrids. Bioorganic & medicinal chemistry letters, 2010, Apr-01, Volume: 20, Issue:7 The synthesis and biological evaluation of two novel series of natural-product-like hybrids based on the chalcone, thiolactone and isatin scaffolds is herein described. Results for a 36-member beta-amino alcohol triazole library showed that the thiolactone-chalcones, with IC(50)s ranging from 0.68 to 6.08 microM, were more active against W2 strain Plasmodium falciparum than the isatin-chalcones with IC(50)s of 14.9 microM or less. Also of interest is falcipain-2 inhibitory activity displayed by the latter, whereas the thiolactone-chalcones lacked enzyme inhibitory activity. Topics: Antimalarials; Chalcone; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Humans; Isatin; Lactones; Malaria, Falciparum; Plasmodium falciparum; Triazoles	2010

Article

Year

CoMFA, CoMSIA, and docking studies on thiolactone-class of potent anti-malarials: identification of essential structural features modulating anti-malarial activity.

Chemical biology & drug design, 2011, Volume: 78, Issue:3

The integrated ligand- and structure-based drug design techniques have been applied on a homogeneous dataset of thiolactone-class of potent anti-malarials, to explore the essential structural features for the inhibition of Plasmodium falciparum. Developed CoMFA (q(2) = 0.716) and CoMSIA (q(2) = 0.632) models well explained structure-activity variation in both the training (CoMFA R(2) = 0.948 & CoMSIA R(2) = 0.849) and test set (CoMFA R(2) (pred) = 0.789 & CoMSIA R(2) (pred) = 0.733) compounds. The docking and scoring of the most active compound 10 into the active site of high-resolution (2.35 Å) structure of FabB-TLM binary complex (PDB-ID: 1FJ4) indicated that thiolactone core of this compound forms bifurcated H-bonding with two catalytic residues His298 and His333, and its saturated decyl side group is stabilized by hydrophobic interactions with the residues of a small hydrophobic groove, illustrating that the active site architecture, including two catalytic histidines and a small hydrophobic groove, is vital for protein-ligand interaction. In particular, the length and flexibility of the side group attached to the position 5 of thiolactone have been observed to play a significant role in the interaction with FabB enzyme. These results present scope for rational design of thiolactone-class of compounds that could furnish improved anti-malarial activity.

Topics: Antimalarials; Drug Design; Humans; Malaria, Falciparum; Models, Molecular; Plasmodium falciparum; Quantitative Structure-Activity Relationship; Thiophenes

2011

Comparison of the antiplasmodial and falcipain-2 inhibitory activity of beta-amino alcohol thiolactone-chalcone and isatin-chalcone hybrids.

Bioorganic & medicinal chemistry letters, 2010, Apr-01, Volume: 20, Issue:7

The synthesis and biological evaluation of two novel series of natural-product-like hybrids based on the chalcone, thiolactone and isatin scaffolds is herein described. Results for a 36-member beta-amino alcohol triazole library showed that the thiolactone-chalcones, with IC(50)s ranging from 0.68 to 6.08 microM, were more active against W2 strain Plasmodium falciparum than the isatin-chalcones with IC(50)s of 14.9 microM or less. Also of interest is falcipain-2 inhibitory activity displayed by the latter, whereas the thiolactone-chalcones lacked enzyme inhibitory activity.

Topics: Antimalarials; Chalcone; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Humans; Isatin; Lactones; Malaria, Falciparum; Plasmodium falciparum; Triazoles

2010