10-Deacetylbaccatin III

10-DAB (also known as 10-Deacetylbaccatin) is an intermediate used for the preparation of taxol, an anti-leukemic and tumor-inhibiting agent isolated from the inner bark of the Pacific yew tree Taxus brevifolia as well as other species of the genus Taxus. Due to the low availability of taxol from its natural sources, 10-DAB is used as a raw material for the preparation of taxol and its derivatives. Being easily extracted from the annual cute of the yew leaves, 10-DAB has a very folded chemical structure with the α hydroxyl group hindered at C-13 easily to form a hydrogen bond with the 4α acetyl group.

Reference

F. Gueritte-Voegelein, V. Senilh, B. David, D. Guenard and P. Potier. Chemical studies of 10-deacetyl baccatin III hemisynthesis of taxol derivatives. Tetrahedron 1986; 42(16): 4451-4460

In vitro activity of 10-deacetylbaccatin III against Leishmania donovani promastigotes and intracellular amastigotes.[Pubmed:17691059]

Planta Med. 2007 Aug;73(10):1081-8.

Current treatments for leishmaniasis are unsatisfactory due to their route of administration, toxicity and expense but, most importantly, to the developed resistance of Leishmania to first-line drugs. Therefore, the identification of new effective targeted drugs is an urgent need. Since many studies have shown that medicinal plants contain compounds active against protozoa we have undertaken a study aiming to determine the antileishmanial activity of the taxoid 10-Deacetylbaccatin III, isolated from dried needles and small branches of the European yew tree (Taxus baccata). Interestingly, 10-Deacetylbaccatin III was found to selectively inhibit the growth of L. DONOVANI intracellular amastigotes within J774 murine macrophages in vitro at nanomolar concentrations with an IC(50) value of 70 nM. Concentrations of 10-Deacetylbaccatin III as high as 5 microM did not affect J774 murine macrophages whereas 20 nM of taxol, used as a control, was toxic to macrophages. The compound also inhibited the growth of L. donovani promastigotes but at higher concentrations with a maximum level of inhibition of 35 %. Taxol inhibited promastigote growth at micromolar concentrations. Comparison of the effect of 10-Deacetylbaccatin III to that of taxol on cell cycle progression and cellular morphology showed that their mechanisms of action are different. The 10-Deacetylbaccatin III-treated promastigotes were slightly arrested in the G2/M phase whereas taxol-treated cells were blocked in the G2/M phase. In addition 10-Deacetylbaccatin III treatment, contrary to taxol, did not affect cellular morphology.

Solid-phase extraction and simplified high-performance liquid chromatographic determination of 10-deacetylbaccatin III and related taxoids in yew species.[Pubmed:11451646]

J Pharm Biomed Anal. 2001 Aug;26(1):89-102.

Solid-phase extraction was accomplished with specially prepared cartridges filled with silanised silica gel (RP-2) for the purpose of 10-Deacetylbaccatin III (10-DAB III) and related taxoids extracts purification obtained from different yew materials. In the first method, the analysed taxoids eluted in 75% methanol, but in the second method, the preliminary elution with 30% methanol was made. DAB III and its six derivatives were separated from co-extractives in merely acetonitrile-water gradient mode during 25 min on Waters Symmetry C-18 column with photodiode array (PDA) detection. The total recoveries for 10-DAB III and paclitaxel in the first SPE method (all compounds were applied in amounts of 80 microg) were about 98 and 94%, respectively. Almost 100% recoveries for paclitaxel and baseline separation of 10-DAB III and co-extracted compounds were obtained when preliminary elution with 30% methanol was performed. This method can be applied as a routine, inexpensive and uncomplicated procedure for 10-DAB III and related taxoids determination in yew material.

Immunological detection and quantitation of 10-deacetylbaccatin III in Taxus sp. plant and tissue cultures.[Pubmed:8060537]

Biol Chem Hoppe Seyler. 1994 Apr;375(4):281-7.

A high-sensitive ELISA method was developed for the detection and semi-quantitative determination of 10-Deacetylbaccatin III and its structurally related compounds in crude extract of Taxus sp. plants and tissue cultures. The antibodies were raised in rabbits using 7- or 10-succinyl-10-Deacetylbaccatin III-BSA conjugate as immunogen. The working range of the assay was from 0.003 to 1.000 ng (0.09 to 31.33 nM) of 10-Deacetylbaccatin III per assay. The cross-reacting material in crude plant extract was examined by chromatographic (silica gel CC, HPLC) and immunoassay methods. Study on the evaluation of cross-reacting material in crude Taxus plant extracts showed that at least 80% of the immunosignal correspond to 10-Deacetylbaccatin III in the extract. The ELISA method was applied to investigate the 10-Deacetylbaccatin III equivalent content in crude extracts of 19 plants species including Taxaceae, Taxodiaceae and Pinaceae species. The 10-Deacetylbaccatin III-like structure was only detected in Taxus and Torreya sp. The results indicate that this immunoassay is a useful tool for the rapid screening of species, varieties or individual plants out of a wide population. The distribution of 10-Deacetylbaccatin III equivalent content in 9-month old Taxus plantlets cultivated in vitro as well as in callus culture was investigated.

[Effects of phenylalanine, sucrose and mannitol on the growth and production of taxol, baccatin III and 10-deacetylbaccatin III in suspension cells of Taxus media].[Pubmed:11938949]

Yao Xue Xue Bao. 1998;33(2):132-7.

The effects of phenylalanine, sucrose and mannitol on the cell growth and the production of taxol, baccatin III and 10-Deacetylbaccatin III in the suspension cells of Taxus media were studied. The results showed that phenylalanine 1.0 mmol.L-1 or 2.0 mmol.L-1 initially added into the medium, and sucrose 73.0 mmol.L-1 and mannitol 173.3 mmol.L-1 added into the medium at the 28th d of culture strongly promoted the cell growth and the formation of the three taxanes in the suspension cells. Compared with those of the control, the cell biomass of the treatments supplemented with phenylalanine and added with sucrose and mannitol at the 28th d of culture increased by 0.6-0.8-fold, taxol yield by 9-10-fold, baccatin III yield by 2.5-3.0-fold, and 10-Deacetylbaccatin III yield by 7-fold. Addition of sucrose 73.0 mmol.L-1 at the 28th d of culture significantly promoted the cell growth, but showed little effect on the contents of the three taxanes in the suspension cultures.