Enhancing Anticancer Potency of a 13-Substituted Berberine Derivative with Cationic Liposomes.

Cationic liposomal formulations of the telomeric G-quadruplex stabilizing ligand, 13-(2-naphthylmethoxy)berberine bromide (1), have been developed with the purpose of delivering 1 into the nucleus of cancer cells for potential telomere targeting. Berberine derivative 1 was encapsulated in various cationic lipids 2-4 by the thin film evaporation method; these lipids are cationic after amine protonation. The most appropriate liposomal berberine formulation was that of 1 and the cholesterol derived cationic lipid 4 in a weight ratio of 1 : 20 with 76.5% encapsulation efficiency of 1. Cellular uptake studies in the HeLa and HT-29 cancer cells lines showed that the liposomal berberine derivative uptake in the cells was higher and more stable than for berberine derivative 1 alone while free 1 was completely decomposed in the cells within 60 min exposure to the cells. Anticancer activity of the liposomal berberine derivative 1 based on 4 was greater than that for the free berberine derivative 1 in the MCF-7, HeLa and HT-29 cell line by 2.3-, 4.9- and 5.3-fold, respectively, and also, interestingly, superior to the anticancer drug doxorubicin against the HT29 cancer cell line.

New flavonoids and xanthone from the stem bark of Artocarpus rigidus blume and cytotoxicity.

Three new flavonoids named artorigidinones A-C and a new xanthone named artorixanthone together with seven known compounds were isolated from the stem bark of Artocarpus rigidus Blume. Their structures were characterized by spectroscopic data. γ-Geranylapigenin exhibited cytotoxicity to a fibroblast-like cell line (SW1353) (IC50 < 0.32 µg/mL) stronger than a standard drug.

Cytotoxic metabolites from the wood-decayed fungus Xylaria sp. BCC 9653.

Chemical investigation of the wood-decayed fungus Xylaria sp. BCC 9653 has led to the isolation of a new methyl aminobenzoate (1) together with eleven known compounds. The structures were established by analysis of spectroscopic data. Cytochalasin D (2), one of the known metabolites, exhibited potent cytotoxicity against African green monkey kidney fibroblast (Vero) cells with an IC(50) value of 0.19 microM.

Paecilodepsipeptide A, an antimalarial and antitumor Cyclohexadepsipeptide from the insect pathogenic fungus Paecilomyces cinnamomeus BCC 9616.

Paecilodepsipeptide A (1), a new cyclohexadepsipeptide possessing three d-amino acid residues, together with its linear analogues paecilodepsipeptides B (2) and C (3), was isolated from the insect pathogenic fungus Paecilomyces cinnamomeus BCC 9616. Structures of these compounds were elucidated primarily by NMR and mass spectroscopic analyses. The absolute configurations of the amino acid and hydroxy acid residues of 1 were addressed by HPLC analysis of its acid hydrolyzate using a chiral column and Marfey's method. Paecilodepsipeptide A (1) showed activity against the malarial parasite Plasmodium falciparum K1 with an IC50 value of 4.9 microM. This compound also showed cytotoxicity to two cancer cell lines, KB (IC50 5.9 microM) and BC (IC50 6.6 microM); however, it was inactive against noncancerous Vero cells up to 67 microM (50 microg/mL).

Antiplasmodial, antimycobacterial, and cytotoxic principles from Camchaya calcarea.

Chemical exploration of Camchaya calcarea (family Compositae) has led to the isolation of nine known sesquiterpene lactones 1 - 9, together with caffeic acid methyl ester 10. Sesquiterpenes 1, 2, 3, 4, 5, 7, and 8 exhibited moderate antiplasmodial activity, but showed potent antimycobacterial activity. Interestingly, the cytotoxicity of sesquiterpene lactones 1, 2, and 4 towards small-cell lung cancer cell line (NCI-H187) is stronger (two orders of magnitude) than towards the Vero cell line. Caffeic acid methyl ester (10) was cytotoxic against NCI-H187 and BC cell lines, however the ester 10 showed only mild antimycobacterial activity.

Cyclohexadepsipeptides from the insect pathogenic fungus Hirsutella nivea BCC 2594.

Two new cyclohexadepsipeptides, hirsutatins A (1) and B (2), were isolated from a culture filtrate of the insect pathogenic fungus Hirsutella nivea BCC 2594. Structures of these compounds were elucidated primarily by NMR and mass spectroscopic analyses. The alpha-carbon stereochemistry of 1 was established by HPLC analysis of its acid hydrolysate using a chiral column. Hirsutatin B (2) exhibited activity against the malarial parasite Plasmodium falciparum K1 with an IC50 value of 5.8 microg/mL, while hirsutatin A (1) was inactive at a concentration of 20 microg/mL.

Micromonosporin A, a novel 24-membered polyene lactam macrolide from Micromonospora sp. isolated from peat swamp forest.

A novel 24-membered polyene lactam macrolide, micromonosporin A (=(3E,5E,7Z,15E,17E,19E,21E)-9,11,13-trihydroxy-14,19,24-trimethyl-1-azacyclotetracosa-3,5,7,15,17,19,21-heptaen-2-one; 1) was isolated from the actinomycete, Micromonospora sp. strain TT1-11, which was isolated from a very acidic peat swamp forest.