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The rearrangements of dihydrobetulin, dihydrobetulinic acid, and abeo-lupane epoxides under acidic conditions (HCl, montmorillonite K10, and BF3·Et2O) were studied. The treatment of dihydrobetulin with HCl or K10 produced abeo-lupane olefins. Their epoxidation afforded epoxides, which, in the presence of protic or Lewis acids, rearranged to dienes or lupanes bearing a bicyclo[3.3.1]nonane fragment. The structure of final products depended on the nature of the catalyst. The HCl promoted 1,4-elimination of water, whereas in the presence of BF3·Et2O bond migration took place preferentially. Montmorillonite K10 favored cyclization to bicyclononane. more...

To improve the properties of cytotoxic triterpenoid acids 1–5, a large set of hydrophilic esters was synthesized. We choose betulinic acid (1), dihydrobetulinic acid (2), 21-oxoacid 3 along with highly active des-E lupane acids 4 and 5 as a model set of compounds for esterification of which the properties needed to be improved. As ester moieties were used - methoxyethanol and 2-(2-methoxyethoxy)ethanol and glycolic unit (type a-d), pyrrolidinoethanol, piperidinoethanol and morpholinoethanol (type f-h), and monosaccharide groups (type i-l). As a result, 56 triterpenic esters (49 new compounds) were obtained and their cytotoxicity on four cancer cell lines and normal human fibroblasts was tested. All new compounds were fully soluble at all tested concentrations, which used to be a problem of the parent compounds 1 and 2. 16 compounds had IC50 more...

Made available in DSpace on 2018-11-26T16:28:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-03-01. Added 1 bitstream(s) on 2019-10-09T18:25:53Z : No. of bitstreams: 1 S0103-50532016000300591.pdf: 2670185 bytes, checksum: bfd14dc581954c8d8f66a13db5bd113a (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) PROPe-UNESP (Young Research) The dihydrobetulinic acid is a known competitive inhibitor of topoisomerase IB from Leishmania donovani, a validated target for developing new antileishmanial drugs. However, its binding mode and interaction pocket have not been established yet. We combined docking and molecular dynamics simulations to identify the most probable binding pocket. Our best model strongly suggests a cavity involving the residues arginine 314 and arginine 410 from chain A, and the catalytic tyrosine 222 from chain B as the interaction site and a substructure of this terpene inhibitor as essential for the process of molecular recognition. Then, a new class of inhibitors with increased affinity could be designed by structure-based approaches. Univ Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, CP 355, BR-14800060 Araraquara, SP, Brazil Univ Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, CP 355, BR-14800060 Araraquara, SP, Brazil FAPESP: 2012/00360-4 more...