Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
SYNTHESIS AND BIOLOGICAL ACTIVITY OF ISOQUINOLINE ANALOGS OF STREPTONIGRIN
Diss Abstr Int [B]; 49(8):3204 1989. Unique Identifier : AIDSLINE ICDB/89655247 Beach JW; Univ. of Florida, FL
Abstract:
Streptonigrin, an antitumor antibiotic isolated from Streptomyces flocculus, is one of the most potent antitumor compounds known. It shows activity against a wide variety of experimental animal tumors as well as several viruses, including herpes simplex I and HTLV III. Its clinical effectiveness was also demonstrated as a single drug or in combination. In addition, the compound is a potent plant growth inhibitor. Streptonigrin has a unique phenyl-pyridylquinoline quinone system with a number of structural elements capable of complexation with divalent ions and this ability serves to play an important role in its activity. A number of structural variations have been made to understand the requirements for activity and most of these were made in rings A, C and D. However, variations of ring B, such as replacement of the quinoline ring by an isoquinoline ring, have not been studied. The present objective was to synthesize a number of 'isoquinoline analogs' and examine their activity using a microbiological assay (B subtilis) and a root growth inhibition assay (cress seedlings). As a first stage, 1-phenyl-6-methoxy-7-aminoisoquinoline-5,8-dione and 1-(2-pyridyl)-6-methoxy-7-aminoisoquinoline-5,8-dione were synthesized using a 10-step sequence. These compounds were found to be equipotent with streptonigrin in the root growth inhibition assay but to be much less potent than streptonigrin in the antibacterial assay. In order to study the effect of the amine function in ring C, the o-, m- and p-aminophenylisoquinolines were synthesized via the corresponding nitro derivatives. Similarly, to study the effect of conjugation in the system, a group of 1-benzylisoquinoline quinones was also prepared. When tested in the root growth inhibition assay, the 1-benzyl and 1-phenylisoquinoline derivatives were found to be equipotent. However, the aminophenylisoquinoline quinones were less potent than the phenylisoquinolines, whereas the corresponding nitrophenylisoquinolines were of greater potency than the phenylisoquinoline. The implications of the structures to metal complexation and hydrogen bonding were discussed. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No: AAD88-17765)
Keywords: Antineoplastic Agents/*PHARMACOLOGY Cell Division/*DRUG EFFECTS Isoquinolines/*PHARMACOLOGY Streptonigrin/*ANALOGS & DERIVATIVES/PHARMACOLOGY Structure-Activity Relationship THESIS 891230
M89C0817
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Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
