Synthesis and antiproliferative activity of some new DNA-targeted alkylating pyrroloquinolines.
Two novel DNA-direct alkylating agents, consisting of aniline mustard linked to an angular 3H-pyrrolo[3,2-f]quinoline nucleus, were synthetized and assayed for their in vitro antiproliferative activity. Simple convergent synthesis, consisting of separate preparation of 9-chloro-3H-pyrrolo[3,2-f]quinoline and p-amino-aniline derivatives, and following their linkage by substitution reactions 8a, b and 10, yielded the corresponding diol derivatives 7b and 9. Biological properties were evaluated with respect to cell growth inhibition, ability to form cross-links with DNA, and capacity to give rise to a molecular complex with the macromolecule for 7b, 8b, 9 and 10.
Ferlin
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MG
Dipartimento di Scienze Farmaceutiche dell'Università di Padova, Via F. Marzolo, 5 35131 Padua, Italy. mariagrazia.ferlin@unipd.it
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D000477:Alkylating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000478:Alkylation / Q000187:drug effects; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012474:Salmon; D013379:Substrate Specificity
D000477:Alkylating Agents; D011758:Pyrroles; D011804:Quinolines; C410406:pyrroloquinoline; D004247:DNA