Pentacyclo-undecane derived cyclic tetra-amines: synthesis and evaluation as potent anti-tuberculosis agents.
As part of an ongoing effort to develop highly potent anti-tuberculosis agents, fourteen pentacyclo-undecane (PCU) tetra-amine compounds were synthesized and screened for their in vitro anti-mycobacterial activity against two TB strains, H37Rv and XDR 194 [an extensively drug-resistant strain of tuberculosis]. Using the broth macrodilution method, nitrofuranylamide based compounds (6a and 6b) showed almost similar activities against the H37Rv strain of Mycobacterium tuberculosis when compared with the control drug, ethambutol. N-Geranyl piperazine PCU (8a) and trans-trans farnesyl piperazine PCU (8b) were 3.2 and 3.7 times more potent than commercially available ethambutol. Both isoprenyl PCU tetra-amine derivatives and N-decyl piperazine PCU (9a) were highly active against the XDR 194 strain of tuberculosis with MICs in the range of 0.63-3.02 microM. Cytotoxicities (IC(50)) of isoprenyl based compounds (8a, 8b) and compound 9a were tested on a mammalian cell line [MDBK (Madin Darby bovine kidney epithelium)] with values of 30, 24 and 25 microM respectively.
Onajole
Oluseye K
OK
School of Chemistry, University of KwaZulu-Natal, Durban, South Africa.
Govender
Karnishree
K
Govender
Patrick
P
van Helden
Paul D
PD
Kruger
Hendrik G
HG
Maguire
Glenn E M
GE
Muthusamy
Karen
K
Pillay
Manormoney
M
Wiid
Ian
I
Govender
Thavendran
T
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D054876:Prenylation
D000473:Alkanes; D000995:Antitubercular Agents; C022884:undecane