PD 114,759 and PD 115,028, novel antitumor antibiotics with phenomenal potency. I. Isolation and characterization.

Bunge, R. H.; Hurley, Timothy R.; Smitka, Tim A.; Willmer, N. E.; Brankiewicz, A. J.; Steinman, C. E.; French, James C.

doi:10.7164/antibiotics.37.1566

Cited by 11 publications

(2 citation statements)

References 2 publications

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“…(ATCC 39363) (1). These unique, sulfur containing compounds have been shown to be extremely potent having IC50 values for the inhibition of tumor cell growth in vitro in the range of 10 -13 -10 -12 M and exhibit antitumor activity against P388 leukemia in vivo at doses ranging from 4-50/zg/kg (1,2). Wilton, G.C.…”

Section: Introductionmentioning

confidence: 99%

Biological and biochemical activities of the novel antitumor antibiotic PD 114,759 and related derivatives

Fry¹,

Shillis²,

Leopold³

1986

Invest New Drugs

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A complex of novel and exceptionally potent antibiotics has been evaluated for antitumor activity in vitro and in vivo and characterized with regard to their ability to cause DNA strand scission. The major component, PD 114,759, was quite active against all in vitro tumor systems including the human tumors, MCF-7 breast, HCT-8 colon, and A549 lung and the murine tumors M16/c mammary, Lewis lung, Pan 02 pancreas and L1210 leukemia. ID50 values ranged from 2-57 pg/ml. In vivo this agent produced significant increases of host life spans in mice bearing L1210 leukemia, B16 melanoma and the M5076 sarcoma. Further, it inhibited growth of subcutaneous implants of the Ridgway osteogenic sarcoma by 80% and growth of the MX-1 human mammary xenograft by 90-95%. PD 114,759, however, had no activity against the colon adenocarcinoma 11a or mammary adenocarcinoma 16c. Chinese hamster ovary cells exposed for 24 hours to concentrations of PD 114,759 ranging from 18 to 37 pg/ml accumulated in the S and G2+M phases of the cell cycle with a corresponding decrease in G1. Higher concentrations of drug apparently stopped any progression through the cell cycle. PD 114,759 caused significant DNA single strand breaks in L1210 cells exposed for 1 hour to drug concentrations as low as 20 pg/ml and the frequency of these lesions increased in proportion to the drug concentration. A portion of these DNA breaks appeared to be associated with protein. In contrast, no double strand DNA breaks were detected at the highest drug concentration tested (100 pg/ml).

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Section: Introductionmentioning

confidence: 99%

Biological and biochemical activities of the novel antitumor antibiotic PD 114,759 and related derivatives

Fry¹,

Shillis²,

Leopold³

1986

Invest New Drugs

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show abstract

“…To our knowledge the N-substituted dimethoxyanthranilate moiety proposed as a partial structure for PD 114,759 and PD 115,028 is unique among microbial products. Although antibiotics of the pyrrolo [ 1,4]benzodiazepine class such as tomaymycin and neothramycin3 contain an anthranilate moiety with the same oxygenation pattern, they are quite unrelated.…”

mentioning

confidence: 99%

The structures of the u.v. chromophoric fragments of the antitumour antibiotics, PD 114,759 and PD 115,028

Wilton¹,

Hokanson²,

French³

1985

J. Chem. Soc., Chem. Commun.

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The chemistry of DNA modification by antitumor antibiotics

Fisher

Aristoff

1988

Progress in Drug Research / Fortschritte Der Arzneimittelforschung / Progrès Des Recherches Pharmaceutiques

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PD 114,759 and PD 115,028, novel antitumor antibiotics with phenomenal potency. I. Isolation and characterization.

Abstract: The isolation of two new antibiotics, PD 114,759 and PD 115,028, exhibiting in vivo antitumor activity at extremely low doses is described. The physico-chemical properties of these sulfur-containing compounds show that they represent a novel class of antitumor agents.

Cited by 11 publications

References 2 publications

Biological and biochemical activities of the novel antitumor antibiotic PD 114,759 and related derivatives

Biological and biochemical activities of the novel antitumor antibiotic PD 114,759 and related derivatives

The structures of the u.v. chromophoric fragments of the antitumour antibiotics, PD 114,759 and PD 115,028

The chemistry of DNA modification by antitumor antibiotics

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