| In vitro: |
| Biochemistry. 2007 Apr 10;46(14):4211-20. | | Totarol inhibits bacterial cytokinesis by perturbing the assembly dynamics of FtsZ.[Pubmed: 17348691] | Totarol, a diterpenoid phenol, has been shown to inhibit the proliferation of several pathogenic Gram-positive bacteria including Mycobacterium tuberculosis.
METHODS AND RESULTS:
In this study, Totarol was found to inhibit the proliferation of Bacillus subtilis cells with a minimum inhibitory concentration of 2 microM. It did not detectably perturb the membrane structure of B. subtilis; it strongly induced the filamentation in B. subtilis cells, suggesting that it inhibits bacterial cytokinesis. Totarol (1.5 microM) reduced the frequency of the Z-ring occurrence per micrometer of the bacterial cell length but did not affect the nucleoid frequency, suggesting that it blocks cytokinesis by inhibiting the formation of the Z-ring. The assembly dynamics of FtsZ is thought to play an important role in the formation and functioning of the Z-ring, a machine that engineers cytokinesis in bacteria. Since Totarol was shown to inhibit the proliferation of M. tuberculosis, we examined the effects of Totarol on the assembly dynamics of M. tuberculosis FtsZ (MtbFtsZ) in vitro. Totarol decreased the assembly of MtbFtsZ protofilaments and potently suppressed the GTPase activity of MtbFtsZ. It bound to MtbFtsZ with a dissociation constant of 11 +/- 2.3 microM. It increased the fluorescence intensity of the MtbFtsZ-1-anilinonaphthalene-8-sulfonic acid complex and inhibited the fluorescence intensity of N-(1-pyrene)maleimide-labeled MtbFtsZ, suggesting that Totarol induces conformational changes in MtbFtsZ. The results indicated that Totarol can perturb the assembly dynamics of FtsZ protofilaments in the Z-ring. Totarol exhibited extremely weak inhibitory effects on HeLa cell proliferation. It did not affect microtubule organization in HeLa cells.
CONCLUSIONS:
The results suggest that Totarol inhibits bacterial proliferation by targeting FtsZ and it may be useful as a lead compound to develop an effective antitubercular drug. | | J Nat Prod. 1992 Oct;55(10):1436-40. | | Antibacterial activity of totarol and its potentiation.[Pubmed: 1453180 ] |
Antimicrobial activity of six diterpenoids isolated from the bark of Podocarpus nagi (Podocarpaceae) has been tested against twelve selected microorganisms.
METHODS AND RESULTS:
Totarol [1], the most abundant compound among the six, exhibited potent bactericidal activity only against Gram-positive bacteria, among which Propionibacterium acnes was the most sensitive bacterium. Totarol also showed strong activity against four other Gram-positive bacteria tested: Streptococcus mutans, Bacillus subtilis, Brevibacterium ammoniagenes, and Staphylococcus aureus (both penicillin-resistant and penicillin-susceptible strains). The bactericidal activity of Totarol was enhanced when it was tested in combination with several other natural products. Noticeably, the activity of Totarol against Sta. aureus was increased eightfold when tested in combination with 1/2MIC of anacardic acid [9]. The synergistic activity of anacardic acid caused the minimum bactericidal concentration (MBC) of Totarol to be lowered from 1.56 to 0.2 micrograms/ml. |
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