Quinone methide chemistry of prekinamycins: 13C-labeling, spectral global fitting and in vitro studies.
In this article, we address the presence of the prekinamycin quinone methide using the techniques of spectral global fitting and the 13C-labeling of the reactive centre. Two-electron reduction of a prekinamycin affords a long-lived quinone methide species that was characterised spectrally. A correlation was made between the calculated DeltaE (kcal/mol) values for quinone methide tautomerisation and cytostatic activity to support the postulate that the quinone methide plays a role in prekinamycin biological activity. We also prepared a stable quinone methide of prekinamycin and studied its solution chemistry directly.
Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-1604, USA.
Omar
O
Khdour
Edward B
EB
Skibo
D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry; D001943:Breast Neoplasms / Q000473:pathology; D002247:Carbon Isotopes / Q000032:analysis / Q000737:chemistry*; D002384:Catalysis; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D045563:Indolequinones / Q000737:chemistry* / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000095602:Angucyclines and Angucyclinones
D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D002247:Carbon Isotopes; D054697:Cytostatic Agents; D045563:Indolequinones; D011809:Quinones; C059018:pre-kinamycin; D000095602:Angucyclines and Angucyclinones; C068040:quinone methide