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Novel Pentamidine Derivatives: Synthesis, Antitumor Properties and Polynucleotide-binding Activities

Jarak, Ivana; Marjanović, Marko; Piantanida, Ivo; Kralj, Marijeta; Karminski-Zamola, Grace (2011) Novel Pentamidine Derivatives: Synthesis, Antitumor Properties and Polynucleotide-binding Activities. European journal of medicinal chemistry, 46 (7). pp. 2807-2815. ISSN 0223-5234

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Abstract

Novel amidino substituted conformationally restricted derivatives of pentamidine were synthesized and their antiproliferative activity against several human cancer cell lines determined. It was found that introduction of furandicarboxamide core moiety (9, 10) increases antiproliferative activity as well as selectivity against certain tumor cell lines in comparison with amidino-substituted furan-mono-carboxamide (5, 6). Unlike the furan series where iso-propyl substituted amidine (10) exhibits more potent overall antiproliferative activity and selectivity toward certain cell lines, the same was found for unsubstituted amidines in pyridine series. Amongst all tested compounds the compound 10 is the only one that possesses antiproliferative activity against SW 620 cell line (4 µM). Spectroscopic studies of the interactions of prepared diamidines with double stranded DNA and RNA polynucleotides show that all compounds preferentially bind into the minor groove of DNA, while most of them intercalate into RNA. The structure-dependant biological activity and the lack of DNA/RNA selective binding suggest that the mechanism of action of the here-presented compounds is controlled not only by the interaction with cellular nucleic acids, but also with other more specific protein targets.

Item Type: Article
Uncontrolled Keywords: dibenzamidine; 2, 5-furandicarboxamide; pentamidine; antitumor evaluation; polynucleotide binding
Subjects: NATURAL SCIENCES > Chemistry
BIOMEDICINE AND HEALTHCARE > Pharmacy
Divisions: Division of Molecular Medicine
Division of Organic Chemistry and Biochemistry
Projects:
Project titleProject leaderProject codeProject type
Dizajn, sinteza i ispitivanje interakcija malih molekula s DNA, RNA i proteinima-Ivo Piantanida098-0982914-2918MZOS
Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA-Marijeta Kralj098-0982464-2514MZOS
Novi heterocikli kao antitumorski i antivirusni (pametni) lijekovi-Marijana Hranjec125-0982464-1356MZOS
Depositing User: Ivo Piantanida
Date Deposited: 13 Dec 2016 12:45
Last Modified: 13 Dec 2016 12:45
URI: http://fulir.irb.hr/id/eprint/1613
DOI: 10.1016/j.ejmech.2011.04.001

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