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Electrochemical DNA Biosensor for Testing Pentamidine and Its Analogues as Potential Chemotherapeutics
Author(s) -
Szpakowska Iwona,
KrassowskaSwiebocka Barbara,
Maciejewska Dorota,
Kazmierczak Pawel,
Jemielita Wirginia,
Konrad Magdalena,
Trykowska Joanna,
MajZurawska Magdalena
Publication year - 2006
Publication title -
electroanalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.574
H-Index - 128
eISSN - 1521-4109
pISSN - 1040-0397
DOI - 10.1002/elan.200603554
Subject(s) - pyridazine , chemistry , pentamidine , nucleic acid , dna , linker , triazine , combinatorial chemistry , substituent , stereochemistry , molecule , pyrimidine , organic chemistry , biochemistry , archaeology , computer science , history , pneumonia , operating system
Electrochemical DNA‐based biosensors are used as screening devices for a rapid evaluation of chemical compounds interacting with double helix of the nucleic acid. Pentamidine is one of minor groove binding chemotherapeutics clinically used as anti‐PCP agent. Therefore, we designed, synthesized and tested some pentamidine analogues with diethyl ether linker and 1,2‐diazine (pyridazine) or 1,3,5‐triazine derivatives with cyanophenoxy substituent, precursors of amidine groups to establish if they can be more efficacious DNA interacting compounds than the original pentamidine drug. The tested compounds were: 1,5‐bis(4‐amidinophenoxy)pentane isethionate‐pentamidine ( 1 ) used as template, 6‐chloro‐3‐(4‐cyanophenoxy)pyridazine ( 2 ), 4,6‐dichloro‐2‐(4‐cyanophenoxy)‐1,3,5‐triazine ( 3 ), 4‐amidinophenol dihydrate ( 4 ), 1,5‐bis(4‐amidinophenoxy)‐3‐oxapentane dihydrochloride‐γ‐oxapentamidine ( 5 ), 1,5‐bis( N ‐cyclohexyl‐4‐amidinophenoxy)‐3‐oxapentane dihydrochloride ( 6 ). The results show that none of the tested analogues binds dsDNA more strongly than the original drug pentamidine ( 1 ). Compound 2 with pyridazine group interacts with the nucleic acid in a different way than the one with triazine ( 3 ) – the signals obtained using DNA‐based biosensor had opposite features. Close derivatives 5 and 6 of the main drug pentamidine ( 1 ) showed a weak influence on the double‐stranded nucleic acid which proves that even small changes in the structure of a molecule can strongly affect the character and properties of the above mentioned compounds in the presence of DNA. In this context atomic charge distribution in the studied molecules is also discussed.