Antimicrobial Activities of Some Actinomycetes Isolated from Different Rhizospheric Soils in Tunisia.

Fifty four isolates of actinomycetes were collected from four different rhizospheric soils: 18 strains from palm tree bark and soil, 12 strains from an olive field soil, 9 strains from a coastal forest, and 15 strains from an agriculture soil situated in the Algerian-Tunisian border (Oum Tboul). Based on morphological and cultural characters, the isolates were classified as Streptomyces (42 strains), Micromonospora (4 strains), Pseudonocardia (1 strain), Actinomadura (1 strain), Nocardia (1 strain), and non-Streptomyces (5 strains). More than half of the isolates inhibited at least one tested pathogenic microorganisms in liquid culture. In addition, antimicrobial activities of some strains were tested on solid culture. Several bioactive compounds were identified by liquid chromatography joined with low-resolution mass spectroscopy (LC/MS) and analysed by MEDINA's database and by the dictionary of natural products Chapman & Hall. An interesting chlorinated compound with the molecular formula C20H37ClN2O4, produced by three different strains (SF1, SF2, and SF5), was subject of an attempted purification. However, it was demonstrated using confocal microscopy and LC/MS high resolution that this compound is produced only on solid culture. These three potential antimicrobial isolates showed high similarity with Streptomyces thinghirensis and Streptomyces lienomycini, in terms of morphological characteristics and 16S rRNA gene sequences (bootstrap 97 %). All these findings prove the high antimicrobial diversity of the studied soils. The potential of the selected and other relatively unexplored extreme environments constitute a source of interesting actinomycete strains producing several biologically active secondary metabolites.

Novel A-ring homodimeric C-3-carbamate analogues of 1alpha,25-dihydroxyvitamin D3: synthesis and preliminary biological evaluation.

The synthesis of a new class of vitamin D3 analogues in which two units of 1alpha,25-dihydroxyvitamin D3 are linked at the C-3 position by a dicarbamate functionality of variable length is described. The analogues demonstrated no affinity for the vitamin D receptor and possessed no antiproliferative or transactivating properties.

Versatile synthesis and biological evaluation of 1,3-diamino-substituted 1alpha,25-dihydroxyvitamin D3 analogues.

A concise route to 1alpha,3beta-diamino-25-hydroxy-3-deoxyvitamin D(3) (5) and 1beta,3alpha-diamino-25-hydroxy-3-deoxyvitamin D(3) (6) has been developed starting from (R)- or (S)-carvone for the construction of the modified A-ring fragments. The conversion of the hydroxyl group to amine function with complete inversion of the configuration was efficiently accomplished by Mitsunobu reaction using phthalimide as nucleophile or activation of the hydroxyl group as mesylate followed by reaction with NaN(3). Diamino 5 and 6 as well as monoamino 3, 4, 30, and 31 vitamin D(3) derivatives have shown poor binding to VDR compared with 1alpha,25-dihydroxyvitamin D(3). The most active compound in the inhibition of MCF-7 cell proliferation and HL 60 cell differentiation was 1alpha-amino analogue 3. Also, very low in vivo calcemic effects of derivatives 3 and 4 were found.

Efficient synthesis of novel 1alpha-amino and 3beta-amino analogues of 1alpha,25-dihydroxyvitamin d(3).

Convenient synthetic routes to 1alpha-amino-25-hydroxyvitamin D(3) (3) and 3beta-amino-3-deoxy-1alpha,25-dihydroxyvitamin D(3) (4), novel analogues of vitamin D(3) bearing an amino group at the C-1 or C-3 position, have been developed starting from (S)-(+)-carvone. Construction of the A-ring fragments was accomplished by selective enzymatic hydrolysis of a diester intermediate and introduction of the amino group under Mitsunobu conditions.