New antiviral antibiotics, kistamicins A and B. I. Taxonomy, production, isolation, physico-chemical properties and biological activities.

A new strain of Microtetraspora parvosata subsp. kistnae subsp. nov. (ATCC 55076) was found to produce new antiviral antibiotics, designated kistamicins A and B. These antibiotics exhibited activity against influenza virus type A and moderate activity against Gram-positive bacteria.

A new neuritogenetic compound BU-4514N produced by Microtetraspora sp.

A novel neuritogenetic compound BU-4514N was isolated from the fermentation broth of Microtetraspora sp. T689-92. It showed significant NGF-mimic activity and antibacterial activity against Gram-positive bacteria. Structural studies revealed that BU-4514N was a new chemotype antibiotic related to lydicamycin.

Pradimicin S, a new pradimicin analog. I. Taxonomy, fermentation and biological activities.

A directed search for antibiotics active in a syncytium formation inhibition assay using a co-culture of HeLa-T4 cells expressing CD4 antigen and BSC-1 cells expressing gp-120 led to the isolation of pradimicin S, a new member of the pradimicin family. The producing strain (AA0851) was characterized as a new species of Actinomadura for which the name Actinomadura spinosa sp. nov. is proposed. Production of pradimicin S by strain AA0851 was significantly improved by addition of ferrous sulfate (0.1-0.4%) to the production medium. Pradimicin S showed potent activity against human immunodeficiency virus (HIV) LAVBRU strain in a CPE assay, and moderate activity against influenza virus type A. The antibiotic was active against a wide variety of fungi and yeasts in vitro and demonstrated in vivo efficacy against a systemic Candida albicans infection in mice.

Terpestacin, a new syncytium formation inhibitor from Arthrinium sp.

Terpestacin, a new antibiotic which inhibits syncytium formation, was isolated from Arthrinium sp. FA1744 (ATCC 74132). The structure of terpestacin was elucidated as a bicyclic sesterterpene on the basis of spectroscopic data and chemical derivatization.

New antiviral antibiotics, cycloviracins B1 and B2. I. Production, isolation, physico-chemical properties and biological activity.

Kibdelosporangium albatum No. R761-7 (ATCC 55061) produced new antiviral antibiotics, cycloviracins B1 and B2. They show weak activity against Gram-positive bacteria and potent antiviral activity against herpes simplex virus type 1. Unique acylsaccharide structures were established for cycloviracins B1 and B2 by degradation and spectroscopic analysis.

Quartromicin, a complex of novel antiviral antibiotics. I. Production, isolation, physico-chemical properties and antiviral activity.

A strain of Amycolatopsis orientalis No. Q427-8 (ATCC 53884) was found to produce a complex of new antiviral antibiotics, quartromicin which consisted of at least six components A1, A2, A3, D1, D2 and D3. Structural studies suggested that they are a novel type of molecules unrelated to any known antibiotics. Each component of quartromicin exhibited antiviral activity against herpes simplex virus type 1, influenza virus type A and human immunodeficiency virus.

Fluvirucins A1, A2, B1, B2, B3, B4 and B5, new antibiotics active against influenza A virus. I. Production, isolation, chemical properties and biological activities.

Five unidentified actinomycete strains produced a series of novel antiviral antibiotics which have a unique 2,6-dialkyl-10-ethyl-3(or 9)-hydroxy-13-tridecanelactam nucleus substituted with 3-amino-3,6-dideoxy-L-talose or 3-amino-3,6-dideoxy-L-mannose(L-mycosamine). The antibiotic components exhibited potent inhibitory activity against influenza virus type A Victoria strain infection in Madin Darby canine kidney cells by the cytopathic effect reduction assay.

Pradimicins A, B and C: new antifungal antibiotics. II. In vitro and in vivo biological activities.

Pradimicins A, B and C specify novel antibiotics produced by Actinomadura hibisca No. P157-2 (ATCC 53557) possessing potent and broad antifungal activity in vivo. They showed moderate in vitro antifungal activity against a wide variety of fungi and yeasts including clinically important pathogens, and were highly effective in systemic infection with Candida albicans in mice after iv and im administrations. Pradimicin A showed in vivo therapeutic activity against C. albicans, Cryptococcus neoformans and Aspergillus fumigatus in both normal and immunocompromized mice. 5-Fluorocytosine- and azole-resistant C. albicans strains were susceptible to pradimicin A. This antibiotic also demonstrated therapeutic efficacy against lung candidiasis and aspergillosis, vaginal candidiasis and skin Trichophyton mentagrophytes infection in mice with iv or topical treatment. The LD50 values after a single iv or im administration were 120 mg/kg and more than 400 mg/kg, respectively. Against various cultured mammalian cells, pradimicin A was noncytotoxic at 100 or 500 micrograms/ml, and showed potent anti-influenza virus activity with an IC50 value of 6.8 micrograms/ml.

Pumilacidin, a complex of new antiviral antibiotics. Production, isolation, chemical properties, structure and biological activity.

New antibiotic pumilacidins A, B, C, D, E, F and G were isolated from the culture broth of a strain of Bacillus pumilus. They are cyclic acylheptapeptide composed of a beta-hydroxy fatty acid, two L-leucine, two D-leucine, L-glutamic acid, L-aspartic acid and L-isoleucine (or L-valine). Pumilacidin components were inhibitory to herpes simplex virus type 1 and H+, K(+)-ATPase and demonstrated antiulcer activity in rat.

Lanthiopeptin, a new peptide antibiotic. Production, isolation and properties of lanthiopeptin.

A strain of Streptoverticillium cinnamoneum produced a peptide antibiotic named lanthiopeptin, which contained four unusual amino acids, erythro-beta-hydroxyaspartic acid, mesolanthionine, threo-beta-methyllanthionine and lysinoalanine. Lanthiopeptin showed antiviral activity against herpes simplex virus type 1 KOS strain infection in Vero cells by cytopathic effect reduction assay. The structure of lanthiopeptin is similar to that of ancovenin.

BMY-28190, a novel antiviral antibiotic complex.

BMY-28190, an antibiotic complex active against herpes simplex virus type 1 (HSV-1) was produced by the cultured broth of Streptoalloteichus hindustanus sp. nov., a producing strain of tallysomycins A and B. The antibiotic complex was recovered from the broth with Amberlite IRC-50 resin and separated from the coproduced tallysomycins and nebramycins by a series of chromatographies. BMY-28190 exhibited weak inhibitory activity toward Gram-positive and Gram-negative bacteria and strong inhibitory activity toward HSV-1. Structural studies disclosed that BMY-28190 is a novel complex of gamma-poly-D-alpha, gamma-diaminobutyric acids with an average MW of 5,130.

Tallysomycin, a new antitumor antibiotic complex related to bleomycin. IV. New biosynthetic derivatives of tallysomycin.

A series of new biosynthetic derivatives of tallysomycins A and B were obtained by precursor amine-feeding fermentation. Certain diamines were incorporated into tallysomycins as the terminal amine moiety affording two classes of biosynthetic derivatives, with or without the Beta-lysine moiety in the subterminal position. Among 21 derivatives prepared, tallysomycin S10b was selected for further studies in view of its favorable therapeutic indices.

Tallysomycin, a new antitumor antibiotic complex related to bleomycin. V. Production, characterization and antitumor activity of tallysomycin S10b, a new biosynthetic tallysomycin derivative.

Tallysomycin S10b is a biosynthetic derivative of tallysomycin B obtained by precursor amine-feeding fermentation. Tallysomycin S10b contains 1,4-diaminobutane as the terminal amine moiety in place of spermidine of tallysomycin B, and its assigned structure was verified by carbon-13 NMR spectrum. The antitumor activity of tallysomycin S10b was comparable to that of tallysomycin A against sarcoma 180 but less active than the latter against leukemia P388. Tallysomycin S10b was less toxic than tallysomycin A in terms of acute and subacute LD50 values. The nephrotoxic potential of tallysomycin S10b in rats was less than that of tallysomycin A.