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Synthesis and cytotoxic activity of substituted 7-aryliminomethyl derivatives of camptothecin.
Eur J Med Chem. 2004 Jun; 39(6):507-13.EJ

Abstract

A series of imines derived from camptothecin-7-aldehyde (CPT-CHO) and aromatic amines were synthesised and tested for their cytotoxicity against tumour cell line H460, that expresses a high level of topoisomerase I. In general ortho-substituted compounds showed higher cytotoxic potency than the corresponding para-substituted imines. This effect was dependent on the nature of the substituent. Structure-activity relationships were studied by calculation of docking energy with a model of the ternary complex camptothecin-DNA-topoisomerase I. The ability of selected compounds to stimulate the topoisomerase I-mediated DNA cleavage and the persistence of the cleavable complex were consistent with the cytotoxic activity.

Authors+Show Affiliations

Dipartimento di Scienze Molecolari Agroalimentari, Sezione di Chimica, Università di Milano, Via Celoria 2, 20133 Milan, Italy. sabrina.dallavalle@unimi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15183909

Citation

Dallavalle, Sabrina, et al. "Synthesis and Cytotoxic Activity of Substituted 7-aryliminomethyl Derivatives of Camptothecin." European Journal of Medicinal Chemistry, vol. 39, no. 6, 2004, pp. 507-13.
Dallavalle S, Merlini L, Morini G, et al. Synthesis and cytotoxic activity of substituted 7-aryliminomethyl derivatives of camptothecin. Eur J Med Chem. 2004;39(6):507-13.
Dallavalle, S., Merlini, L., Morini, G., Musso, L., Penco, S., Beretta, G. L., Tinelli, S., & Zunino, F. (2004). Synthesis and cytotoxic activity of substituted 7-aryliminomethyl derivatives of camptothecin. European Journal of Medicinal Chemistry, 39(6), 507-13.
Dallavalle S, et al. Synthesis and Cytotoxic Activity of Substituted 7-aryliminomethyl Derivatives of Camptothecin. Eur J Med Chem. 2004;39(6):507-13. PubMed PMID: 15183909.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and cytotoxic activity of substituted 7-aryliminomethyl derivatives of camptothecin. AU - Dallavalle,Sabrina, AU - Merlini,Lucio, AU - Morini,Gabriella, AU - Musso,Loana, AU - Penco,Sergio, AU - Beretta,Giovanni Luca, AU - Tinelli,Stella, AU - Zunino,Franco, PY - 2003/11/24/received PY - 2004/02/25/revised PY - 2004/02/25/accepted PY - 2004/6/9/pubmed PY - 2005/2/16/medline PY - 2004/6/9/entrez SP - 507 EP - 13 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 39 IS - 6 N2 - A series of imines derived from camptothecin-7-aldehyde (CPT-CHO) and aromatic amines were synthesised and tested for their cytotoxicity against tumour cell line H460, that expresses a high level of topoisomerase I. In general ortho-substituted compounds showed higher cytotoxic potency than the corresponding para-substituted imines. This effect was dependent on the nature of the substituent. Structure-activity relationships were studied by calculation of docking energy with a model of the ternary complex camptothecin-DNA-topoisomerase I. The ability of selected compounds to stimulate the topoisomerase I-mediated DNA cleavage and the persistence of the cleavable complex were consistent with the cytotoxic activity. SN - 0223-5234 UR - https://www.unboundmedicine.com/medline/citation/15183909/Synthesis_and_cytotoxic_activity_of_substituted_7_aryliminomethyl_derivatives_of_camptothecin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223523404000546 DB - PRIME DP - Unbound Medicine ER -