Funiculosin, a new antibiotic. II. Structure elucidation and antifungal activity.

Mitochondrial cytochrome b: evolution and structure of the protein

“…Correlations between an unusual response to one bc 1 inhibitor and the sequence of the cytochrome b protein are most convincing when they combine sequence analysis in related s p e o e s with the information derived from mutants In the case of the natural resistance of fish to fumculosln [90], the results of a selected screening of fumculosin sensitivity m animal m l t o c h o n d n a suggested that the substitution of the conserved alanme 126 with the bulky m e t h l o n m e in the fish protein (Fig 1) is probably responsible for a substantial increase m the tltre of this inhibitor relatwe to normally sensltwe s p e o e s (Table V and R e f 90) Natural resistance in the plant mItochondnal bc t complex [142] could also be correlated with the exchange of A126 with the bulkier V m the cytochrome b sequence (Fig 2 and R e f 90) The buried location of position 126 within the transmembrane sector of hehx C (Fig 1) may account for the 'hybrid' effects of fumculosln, which effects both center i and center o [90,114,[143][144][145][146] Note that the proteins having a bulky amino a o d at poslt~on 126 also show resistance to U H D B T (Table V), which xs a center o inhibitor that shares with funlculosm the property of effectlng both qulnone sites [113,114,143,144] An interesting property of funlculosln is its remarkable species specificity, even among mammals [143,147] The volume pattern and the comparison of the sequences of sensltwe and resistant species suggested previously that position 194 may also be revolved in funlculosln binding [90] By inspecting the aligned sequences, we noticed that the rabbit protein shows the substitution of alanine 194 with a bulkier vahne residue (Fig 1) Hence, rabbit mltochondrla were expected to be quite resistant to funlculosin, which would explain why rabbits are resistant to this drug in vwo [147] This ~s indeed the case, since the inhibitory potency of funlculosln on the ublqumol cytochrome c reductase actwlty is about 60-fold lower for m l t o c h o n d n a ~solated from rabbit than those from sensltwe mammals (Table V) The cytochrome b proteins of zebra and donkey also have vahne at position 194 (Fig 1 and R e f 32) and differ from that of pig, a...…”

Penicillium and Acremonium

“…(Sassa et al, 1974) Me Funicu10sin (371) P. funiculosum (Ando et al, 1978) Is1andic acid (373) P. islandicum (Fujimoto et al, 1982) 2,2'-Methy1enebis( 5-methy1-6-tert-buty1pheno1) (374) P.janthinellum (Nakakita etal., 1984b) Paraherquonin (375) P. simplicissimum (Okuyama etal., 1983) Antibiotic 2188 (376) P. rugulosum (German patent, 1984) (Okuda et al, 1984) HO Penicillium sp. U apanese patent, 1985)…”

Synthesis of Acetyl and Iodo Derivatives of 4‐Hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]pyridine‐2,5‐diones and 4‐Hydroxy‐1‐phenylpyridin‐2(1H)‐ones

“…The chemistry of 4‐hydroxy‐2(1 H )‐pyridone has been attracting considerable attention because of several reasons. A number of natural products containing this moiety are available, having various biological properties . Because 4‐hydroxy‐2‐pyridones may also exist in their tautomeric 2‐hydroxy‐4‐pyridone form , this aspect has found attention.…”