Novel pentamidine derivatives: Synthesis, anti-tumor properties and polynucleotide-binding activities

Abstract

Novel amidino substituted conformationally restricted derivatives of pentamidine were synthesized and their antiproliferative activity against several human cancer cell lines determinated. 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 herepresented compounds is controlled not only by the interactions with cellular nucleic acids, but also with other more specific protein targets.

Antimutagenic and antioxidant activity of novel 4-substituted phenyl-2,2'-bichalcophenes and aza-analogs

“…Several pentamidine derivatives have antiproliferative activity against several human cancer cell lines 2,3. However, these exhibit a number of serious side effects, toxicity problems, and poor availability 4.…”

New Pentamidine Analogues in Medicinal Chemistry

“…Amidino-substituted conformationally restricted derivatives of pentamidine were synthesized (Scheme 27) [68]. It was found that introduction of furandicarboxamide core moiety (97, 98) antiproliferative activity as well as selectivity against certain tumor cell lines in comparison with amidino-substituted furan-mono car-boxamide.…”

Bis[2-(4-aminophenyl)-4,5-dihydro-1H-imidazol-3-ium] dichloride monohydrate

“…For background and the biological activity of aromatic amidines, see: Chen et al (2010); Hu et al (2009); Del Poeta et al (1998); Baraldi et al (2004); Jarak et al (2011); Neidle (2001); Stolić et al (2011). For the synthesis, see Widra et al (1990).…”