Disease relevance of Totarol

• The antimicrobial mechanism of totarol was studied using Pseudomonas aeruginosa IFO 3080 [1].
• None of the analogues was more potent than totarol itself, which is effective against these gram-positive bacteria at MIC values of 7 microM [2].
• The inhibitory and bactericidal activities of anacardic acid and totarol, alone and in combination with methicillin, were investigated against methicillin-resistant Staphylococcus aureus (MRSA) [3].
• Furthermore, totarol protected red cells against oxidative hemolysis [4].

High impact information on Totarol

• The site of respiratory inhibition of totarol was thought to be near CoQ in the bacterial electron transport chain [1].
• NADH-cytochrome c reductase was inhibited by totarol while cytochrome c oxidase was not [1].
• Compounds that showed the greatest cytotoxicity towards AGS cells were ferruginol (2), the corresponding formate (5), acetate (6), propionate (7), 8, 9, 12-(beta-D-glucopyranosyloxy)-abieta-8,11,13-triene (16), 18 and totarol (20) (IC50 18-44 muM) [5].
• In order to obtain active compounds with less cytotoxicity, 18 semisynthetic ferruginol derivatives and totarol were assessed for their gastroprotective effects in the HCl/ethanol-induced gastric lesion model in mice, as well as for cytotoxicity in human gastric epithelial cells (AGS) and human lung fibroblasts (MRC-5) [5].
• Two new diterpene anticancer constituents termed nootkastatins 1 (4) and 2 (5) were isolated along with three previously known diterpene cancer cell growth inhibitors where two were reported as synthetic modifications of totarol and not previously found in nature [6].

Chemical compound and disease context of Totarol

• Nisin, lauricidin, and totarol were only effective against the Gram-positive bacteria [7].

Biological context of Totarol

• A series of analogues of, and potential pro-drugs derived from, the potent antibacterial diterpene totarol (1) were synthesized in order to elucidate the minimum structural requirements for antibacterial activity and to seek compounds with good bioavailability in vivo [2].
• Totarol (1) was shown to uncouple oxidative phosphorylation in isolated mitochondria at 50 microM [8].

Anatomical context of Totarol

• Initially, a microtiter plate growth assay was used to determine the inhibitory concentrations of four "natural" antimicrobials (nisin, lauricidin, totarol, and the lactoperoxidase system (LPS)) against a panel of eight bacteria [7].

Associations of Totarol with other chemical compounds

• We conclude that the primary staphylococcal target for totarol is the respiratory chain, but that potentiation of methicillin by diterpenes is by interference with PBP 2a expression [9].

Gene context of Totarol

• The synthesis and antibacterial activity of totarol derivatives. Part 1: modifications of ring-C and pro-drugs [2].
• A diterpenoid, totarol (1), from Podocarpus nagi was evaluated as an antioxidant [4].

References