Archazolids, New Cytotoxic Macrolactones from Archangium gephyra (Myxobacteria). Production, Isolation, Physico‐chemical and Biological Properties.

Abstract

Archazolids, New Cytotoxic Macrolactones from Archangium gephyra (Myxobacteria). Production, Isolation, Physico-chemical and Biological Properties. -The new cytotoxic compounds archazolid A and B (I) are isolated from the culture broth of strains of the myxobacteria Archangium gephyra and Cystobacter sp. The data indicate that archazolid is an inhibitor of the V-ATPase of higher cells. -(SASSE*, F.; STEINMETZ, H.; HOEFLE, G.; REICHENBACH, H.; J. Antibiot. 56 (2003) 6, 520-525; Abt. Naturstoffbiol., Ges. Biotechnol. Forsch. mbH, D-38124 Braunschweig, Germany; Eng.) -M. Bohle 46-219

Selective upregulation of TNFα expression in classically-activated human monocyte-derived macrophages (M1) through pharmacological interference with V-ATPase

“…Archazolid B was isolated from Archangium gephyra as previously described [14]. Apicularen A was from the natural compound library of HZI/HIPS (Braunschweig, Germany).…”

“…Here, we aimed to obtain insights into the role of V-ATPase in cytokine and chemokine secretion from human macrophages derived from peripheral blood monocytes, taking into account macrophage plasticity and occurrence as different phenotypes. As a suitable tool to studying the role of V-ATPase we used the myxobacterial compound archazolid [14] that binds to V-ATPase [15][16][17]. Archazolid has been intensively investigated as anti-tumoral agent that induced apoptosis of cancer cells and reduced migration of invasive tumor cells in vitro, and decreased metastatic dissemination of breast tumors in vivo [18][19][20].…”

Targeting V-ATPase in primary human monocytes by archazolid potently represses the classical secretion of cytokines due to accumulation at the endoplasmic reticulum

“…Archazolid B was isolated from Archangium gephyra as described [18]. Apicularen A was obtained from the natural compound library of HZI/HIPS (Braunschweig, Germany).…”

The First Hydroxylated Archazolid from the Myxobacterium Cystobacter violaceus: Isolation, Structural Elucidation and V-ATPase Inhibition

“…Fermentation of C. violaceus strain Cb vi105, isolated at the HZI, in the presence of 3 liter Amberlite XAD-16 adsorber resin for 10 days at 30°C and preparation of the crude extract (13.7 g) from the adsorber resin proceeded according to previously reported procedures [2,7]. 4 was isolated and purified from the crude extract by gel chromatography on Sephadex LH 20 (Fluka Steinheim, solvent: methanol, flow 7 ml/minute), reversed-phase MPLC (solvent: methanol/waterϭ8 : 2, detection 230 nm, flow 65 ml/minute) and high pressure RP chromatography (solvent: acetonitrile/waterϭ65/35, detection 230 nm, flow 15 ml/minute).…”

“…) and B (2) [2] are a structurally novel type of particularly efficient V-ATPase inhibitors with IC 50 values in the low nanomolar range, both in vitro [3] and in vivo [2]. It has been demonstrated that 1 binds to the membrane bound V o subunit c in a reversible non-covalent manner [3].…”