Synthesis and biological evaluation of ( − )-13,14-dihydroxy-8,11,13-podocarpatrien-7-one and derivatives from (+)-manool

Abstract

13,14-Dihydroxy-8,11,13-podocarpatrien-7-one (1) and a series of ring C aromatic diterpene derivatives were synthesised from (+)-manool (4) and evaluated for their cytotoxic, leishmanicidal and trypanocidal activities. Our results indicated that compound 1 and other podocarpane-type intermediates are cytotoxic. Cleavage of C6-C7 bond of compound 7 improved cytotoxic activity, indicating that, in particular, the 6,7-seco-podocarpane-type compound 20 might serve as a lead compound for further development.

Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca2+ release in Leishmania mexicana promastigotes

“…To determine the IC 50 in parasites and human fibroblasts the protocol described by 37 was followed. Briefly, a suspension of 2 x 10 6 parasites per mL -1 or 5 x 10 3 fibroblasts per well were transferred into 96 well plates and different concentrations of the compounds were added.…”

Synthesis of Novel Podocarpa-8,11,13-Triene-7- and 13-Nitriles and Evaluation of their Anti-Inflammatory and Cytotoxic Activity

“…According to the procedure previously reported by us, the key intermediate 2 was obtained in two steps from (+)-manool 1, via ozonolysis 16 and intramolecular condensation, 17 and intermediate 3 was obtained in three steps from compound 2, via aromatisation, 16 protection 18 and benzylic oxidation. 18 Reaction of 3 with trimethylsilyl cyanide (TMSCN) in the presence of the KCN/18-crown-6 complex at room temperature for 8 h (Method A) followed by dehydration with POCl 3 gave compound 4 in 70% yield. However, reaction of 3 with TMSCN using molecular iodine as a catalyst at room temperature for 90 min (Method B) followed by dehydration with POCl 3 yielded compound 4 in 84% yield.…”

“…Benzylic oxidation of compound 8 using pyridinium dichromate (PDC), t-BuO 2 H and Celite in benzene was used to obtain 9. 18 Then, employing SeO 2 , CH 3 CO 2 H and H 2 O in 1,4-dioxane at reflux, 18 the α,βunsaturated ketone 10 was formed.…”

“…16,17 (2 reaction steps); (ii) Ref. 16,18 activity in RAW 264.7 cells in the range of concentrations evaluated, as well as weak cytotoxic activity in HT-29 and PC3 cells. Thus, the inhibitory activity of the compound 9 could represent a new lead structure for the design of drug candidates against inflammatory diseases.…”