Trichormamides A and B with Antiproliferative Activity from the Cultured Freshwater Cyanobacterium Trichormus sp. UIC 10339

Abstract

Two new cyclic lipopeptides, trichormamides A (1) and B (2), were isolated from the cultured freshwater cyanobacterium Trichormus sp. UIC 10339. The strain was obtained from a sample collected in Raven Lake in Northern Wisconsin. The planar structures of trichormamides A (1) and B (2) were determined using a combination of spectroscopic analyses including HRESIMS and 1D and 2D NMR experiments. The absolute configurations of the amino acid residues were assigned by the advanced Marfey’s method after acid hydrolysis. Trichormamide A (1) is a cyclic undecapeptide containing two d-amino acid residues (d-Tyr and d-Leu) and one β-amino acid residue (β-aminodecanoic acid). Trichormamide B (2) is a cyclic dodecapeptide characterized by the presence of four nonstandard α-amino acid residues (homoserine, N-methylisoleucine, and two 3-hydroxyleucines) and one β-amino acid residue (β-aminodecanoic acid). Trichormamide B (2) was cytotoxic against MDA-MB-435 and HT-29 cancer cell lines with IC50 values of 0.8 and 1.5 μM, respectively.

Trichormamides C and D, antiproliferative cyclic lipopeptides from the cultured freshwater cyanobacterium cf. Oscillatoria sp. UIC 10045

“…The stereoisomers of N MeIle and 3-OHLeu were synthesized as previously described. 7 This allowed for assignment of l configurations for Thr1/2 and N MeIle, and 2 R , 3 S configurations for 3-OHLeu1/2. Therefore, the complete structure of trichormamide C ( 1 ) was determined as cyclo[ l -Thr- d -Leu- l -Pro- l -Thr- d -Asn- l - N MeIle- l -Gln–(2 R ,3 S )-3-OHLeu– l -Ala– (2 R ,3 S )-3-OHLeu– l -Val–(3 R )-Ada].…”

“…For example, hormothamnin A was obtained from the tropical marine species Hormothamnion enteromorphoides ; 18 laxaphycins were isolated from a marine species Anabaena torulosa and a terrestrial species Anabaena laxa ; 14,19,20 trichormamides A and B were isolated from a freshwater strain Trichormus sp. 7 These strains all belong to the order of Nostocales . In contrast, lobocyclamides were isolated from a marine Lyngbya confervoides , 13 and lyngbyacyclamides were isolated from a marine Lyngbya sp.…”

“…Each hydrolysate was separated into two equal portions for derivatization with either l - or dl -FDLA (1-fluoro-2,4-dinitrophenyl-5-leucinamide) using established protocols. 7 LC-MS analysis was performed using a reversed-phase column (Phenomenex Kinetex C 18 , 250 × 4.6 mm, 5 µm, 1.0 mL/min) with a linear gradient from 25% to 65% CH 3 CN in H 2 O with 0.1% formic acid over 50 min. The absolute configurations of amino acid residues were assigned based on the retention times of l -FDLA and dl -FDLA derivatives of each amino acid in the extracted ion chromatograms (EIC).…”

Discovery of Anticancer Agents of Diverse Natural Origin

“…Trichormamide B, a cyclic dodecapeptide, displayed cytotoxic activity against the MDA-MB-435 and HT-29 cell lines with IC 50 values of 0.8 and 1.5 μM, respectively. Trichormamide A, a cyclic undecapeptide, was less potent than trichormamide B and exhibited IC 50 values of 9.9 and 16.9 μM against MDA-MB-435 and HT-29 cells, respectively (102). …”

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status

“…[48], Northern Wisconsin cyanobacterium Trichormus sp. UIC 10339 [49], toxic cyanobacterium Nostoc sp. 152 [50], Kenyan cyanobacterium Lyngbya majuscule [51], mollusks like Papua New Guinea mollusk (sea hare) Dolabella auricularia [52] and alga like Indonesian red alga (Rhodophyta) Ceratodictyon spongiosum containing the symbiotic sponge Sigmadocia symbiotica [10].…”