A new pentacyclic triterpenoid, 3,25-epoxy-3,22,23-trihydroxy-olean-12-en-28-oic acid (1), together with seven known compounds, including five triterpenoids, -amyrin (2), lantadene B (3), lantanilic acid (4), lantanolic acid (5) and ursolic acid (6) in addition to -sitosterol (7) and benzoic acid (8) has been isolated from the leaves of Lantana montevidensis. Their chemical structures were elucidated by spectroscopic analysis and by comparison with the literature data and/or authentic samples. Compound 1 showed moderate to weak antibacterial activity against Staphylococcus aureus and Escherichia coli.

A new pentacyclic triterpenoid, 3,25-epoxy-3,22,23-trihydroxy-olean-12-en-28-oic acid (1), together with seven known compounds, including five triterpenoids, -amyrin (2), lantadene B (3), lantanilic acid (4), lantanolic acid (5) and ursolic acid (6) in addition to -sitosterol (7) and benzoic acid (8) has been isolated from the leaves of Lantana montevidensis. Their chemical structures were elucidated by spectroscopic analysis and by comparison with the literature data and/or authentic samples. Compound 1 showed moderate to weak antibacterial activity against Staphylococcus aureus and Escherichia coli.

A new pentacyclic triterpenoid, 3,25-epoxy-3,22,23-trihydroxy-olean-12-en-28-oic acid (1), together with seven known compounds, including five triterpenoids, -amyrin (2), lantadene B (3), lantanilic acid (4), lantanolic acid (5) and ursolic acid (6) in addition to -sitosterol (7) and benzoic acid (8) has been isolated from the leaves of Lantana montevidensis. Their chemical structures were elucidated by spectroscopic analysis and by comparison with the literature data and/or authentic samples. Compound 1 showed moderate to weak antibacterial activity against Staphylococcus aureus and Escherichia coli.

A new pentacyclic triterpenoid, 3,25-epoxy-3,22,23-trihydroxy-olean-12-en-28-oic acid (1), together with seven known compounds, including five triterpenoids, -amyrin (2), lantadene B (3), lantanilic acid (4), lantanolic acid (5) and ursolic acid (6) in addition to -sitosterol (7) and benzoic acid (8) has been isolated from the leaves of Lantana montevidensis. Their chemical structures were elucidated by spectroscopic analysis and by comparison with the literature data and/or authentic samples. Compound 1 showed moderate to weak antibacterial activity against Staphylococcus aureus and Escherichia coli.

4-(4-Phenoxybenzoyl)benzoic acid derivatives (PBADs) were found to inhibit rat and human alpha-reductase isozymes 1 and 2 in vitro. Chemiluminescence (CL), electron spin resonance, spin trapping techniques, and spectrophotometry were used to examine the effect of PBADs on reactive oxygen species (superoxide radical, O(2)(.-); hydroxyl radical, HO(*); singlet oxygen, (1)O(2)) generating systems. All test compounds at a concentration of 0.5 mM enhanced the CL from O(2)(.-) up to fivefold, which was recorded as the light sums during 1 min. At 0.38 mM PBAD enhanced production of HO(*) from H(2)O(2) in the presence of Co(II) up to 90%, as measured by a deoxyribose assay. Using the spin trap agent 5,5-dimethyl-1-pyrroline-N-oxide, it was found that the amplitude of the signal arising from the Fenton-like reaction [Co(II)/H(2)O(2)] was significantly diminished by the test compounds. The compounds also inhibited the (1)O(2) dependent 2,2,6,6-tetramethylpiperidine-N-oxide radical, which is generated in the acetonitrile/H(2)O(2) system. The measured rate constants of (1)O(2)-dimol quenching by PBAD were in the range of (0.8-2.6) x 10(8) M(-1) s(-1). The interaction between PBAD and (1)O(2) was also checked using a spectrophotometry method based on bleaching of p-nitrosodimethylaniline. These results indicate that PBAD may directly scavenge HO(*) and (1)O(2), but not O(2)(.-). However, the compounds that were examined had prooxidant ability under some reaction conditions.

In search of novel nonsteroidal mimics of steroidal inhibitors of 5 alpha reductase, 4-(2-phenylethyl)cyclohex-1-ene carboxylic acids 1-5 were synthesized with different substituents in para position of the phenyl ring (1: N, N-diisopropylcarbamoyl, 2: phenyl, 3: phenoxy, 4: benzoyl, and 5: benzyl). The principal synthetic approach for the desired compounds consisted of a Wittig olefination between 1, 4-dioxaspiro [4.5]-decane-8-carbaldehyde (4g and the appropriate phosphonium salts. The compounds were tested for inhibition of human 5 alpha reductase isozymes 1 and 2 using DU 145 cells and preparations from prostatic tissue, respectively. They turned out to be good inhibitors of the prostatic isozyme 2 with compound 1 being the most potent one (IC(50) = 760 nM). Isozyme 1 was only slightly inhibited. It is concluded that the novel structures are appropriate for being further optimized, aiming at the development of a novel drug for the treatment of benign prostatic hyperplasia.

Novel 3,4-dihydro-naphthalene-2-carboxylic acids were synthesized and evaluated for 5alpha reductase inhibitory activity. This enzyme exists in two isoforms and is a pharmacological target for the treatment of benign prostatic hyperplasia, male pattern baldness and acne. In the present study non-steroidal compounds capable of mimicking the transition state of the steroidal substrates were prepared. The synthetic strategy for the preparation of compounds 1-6 consisted of triflation followed by subsequent Heck-type carboxylation or methoxy carbonylation for 6-phenyl-3,4-dihydronaphthalen-2(1H)-one 1c. A Negishi-type coupling reaction between 6-(trifluoro-methanesulfonyloxy)-3,4-dihydro-naphthalene-2-carboxylic acid methyl ester 7b and various aryl bromides led, after further transformations, to 6-substituted 3,4-dihydro-naphthalene-2-carboxylic acids 7-15. In a similar way the corresponding naphthalene-2-carboxylic acids 16 and 17 were obtained. The DU 145 cell line and prostate homogenates served as enzyme sources for the human type 1 and type 2 isozymes, whereas ventral prostate was employed to evaluate rat isozyme inhibitory potency. The most active inhibitors identified in this study were 6-[4-(N,N-dicyclohexylaminocarbonyl)phenyl]-3,4-dihydro-naphthalene-2-carboxylic acid (3) (IC50 = 0.09 microM, rat type 1), 6-[3-(N,N-dicyclohexylaminocarbonyl)phenyl]-3,4-dihydro-naphthalene-2-carboxylic acid (13) (IC50 = 0.75 microM, human type 2; IC50 = 0.81 microM, human type 1) and 6-[4-(N,N-diisopropylamino-carbonyl)phenyl]naphthalene-2-carboxylic acid (16) (IC50 = 0.2 microM, human type 2). The latter compound was shown to deactivate the enzyme in an uncompetitive manner (Ki = 90 nM; Km, Testosterone = 0.8-1.0 microM) similar to the steroidal inhibitor Epristeride. Select inhibitors (13 and 16) were tested in vivo using testosterone propionate-treated, juvenile, orchiectomized SD-rats. None of the compounds was active at a dose of 25 mg/kg. This result might in part be ascribed to the relatively poor in vitro rat isozyme inhibitory potency.