An alignment independent 3D QSAR study of the antiproliferative activity of 1,2,4,5-tetraoxanes.
An alignment-free 3D QSAR study on antiproliferative activity of the thirty-three 1,2,4,5-tetraoxane derivatives toward two human dedifferentiated cell lines was reported. GRIND methodology, where descriptors are derived from GRID molecular interaction fields (MIF), were used. It was found that pharmacophoric pattern attributed to the most potent derivatives include amido NH of the primary or secondary amide, and the acetoxy fragments at positions 7 and 12 of steroid core which are, along with the tetraoxane ring, common for all studied compounds. Independently, simple multiple regression model obtained by using the whole-molecular properties, confirmed that the hydrophobicity and the H-bond donor properties are the main parameters influencing potency of compounds toward human cervix carcinoma (HeLa) and human malignant melanoma (FemX) cell lines. Corollary, similar structural motifs are found to be important for the potency toward both examined cell lines.
Cvijetić
Ilija N
IN
Faculty of Chemistry, University of Belgrade, Studentski Trg 12-16, 11000 Belgrade, Serbia.
Zizak
Zeljko P
ZP
Stanojković
Tatjana P
TP
Juranić
Zorica D
ZD
Terzić
Natasa
N
Opsenica
Igor M
IM
Opsenica
Dejan M
DM
Juranić
Ivan O
IO
Drakulić
Branko J
BJ
D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008545:Melanoma / Q000188:drug therapy; D008954:Models, Biological; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D045568:Tetraoxanes / Q000737:chemistry* / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D000962:Antimalarials; D000970:Antineoplastic Agents; D045568:Tetraoxanes