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

Jarak, Ivana; Marjanović, Marko; Piantanida, Ivo; Kralj, Marijeta; Karminski‐Zamola, Grace

doi:10.1016/j.ejmech.2011.04.001

Cited by 30 publications

(13 citation statements)

References 29 publications

(34 reference statements)

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

El‐Sayed¹,

Hussin²

2013

DDDT

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Evaluation of the potential antimutagenic activities of new compounds by Ames assay has been of great interest for the development of novel therapeutics for many diseases including cancer. Ten novel bichalcophenes with in vitro and in vivo broad spectrum activities against various microbial strains were investigated throughout the present study for their cytotoxic, antioxidant, and antimutagenic potential in a Salmonella reverse mutation assay system against sodium azide (NaN3) and benzo[a]pyrene (B[a]P). At nontoxic concentrations, all bichalcophenes alone or in combination with NaN3 (1 μg/plate) or B[a]P (20 μM) with S9 mix were not mutagenic. The bichalcophenes significantly reduced NaN3- and B[a]P-induced mutagenicity under pre-exposure and co-exposure conditions in a concentration-independent manner. However, the antimutagenic activity of bichalcophenes against B[a]P varied depending on the exposure regimen, being more effective under pre-exposure conditions. The antimutagenic activity was correlated with a high antioxidant activity that could promote the DNA repair system. Bichalcophenes are least likely to interfere with the microsomal bioactivation of B[a]P. Monocationic bichalcophenes were superior to the corresponding mononitriles as antimutagenic agents against both mutagens investigated, possibly due to the higher nucleophilic centers they have which could bind and protect the bacterial DNA. Three monocationic compounds were shown to have a strong anticancer activity against the 58 cell line. Based on the results of the present investigation, monocationic compounds (1, 4, and 5B) will be selected for further time consuming and costly chemoprevention studies in animal models.

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Section: Introductionmentioning

confidence: 99%

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

El‐Sayed¹,

Hussin²

2013

DDDT

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“…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.…”

Section: Cnmentioning

confidence: 99%

New Pentamidine Analogues in Medicinal Chemistry

Porcheddu¹,

Giacomelli²,

Luca³

2012

CMC

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Sixty years after its introduction, 1,5-bis(4-amidinophenoxy)pentane (Pentamidine) is still one of the most used drugs for the treatment of the first stage of Human African trypanosomiasis and other neglected diseases such as malaria and leishmaniasis. These protozoan infections are prevalent in the poorest world areas such as sub-saharian and developing countries, however the increasing immigration from these countries to the richest part of the world and the overlap of HIV with parasitic infections result in a growing number of cases in developed nations. A great effort has been made to develop new generations of diamidines for the treatment of these infections transmitted by insects. This review summarises the synthesis and evaluation of pentamidine analogues reported in the last years in the effort to find new drugs with better pharmaceutical activity, higher lipophilicity and lower citotoxycicty.

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“…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).…”

Section: Related Literaturementioning

confidence: 99%

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

et al. 2011

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The asymmetric unit of the title compound, 2C9H12N3 +·2Cl−·H2O, comprises two molecules, two chloride anions and one molecule of crystal water. In the imidazolinium ring, the protonation contributes to delocalization of the positive charge over the two C—N bonds. Both chloride anions are acceptors of four hydrogen bonds in a flattened tetrahedron environment. The donors are NH2 groups, the NH groups of the imidazolinium rings and the water molecule. These hydrogen bonds and N—H⋯O(H2O) hydrogen bonds form a three-dimensional network.

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

Cited by 30 publications

References 29 publications

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

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

New Pentamidine Analogues in Medicinal Chemistry

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

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

Cited by 30 publications

References 29 publications

Antimutagenic and antioxidant activity of novel 4-substituted phenyl-2,2&#39;-bichalcophenes and aza-analogs

Antimutagenic and antioxidant activity of novel 4-substituted phenyl-2,2&#39;-bichalcophenes and aza-analogs

New Pentamidine Analogues in Medicinal Chemistry

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

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Product

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

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