- Easy, safe, and effective novel methods for preparing either (diacetoxyiodo)-arenes, ArI(OAc)2, or iodylarenes, ArIO2, from the corresponding iodoarenes, ArI, using sodium periodate as the oxidant are presented in this paper. In order to obtain 2- and 4-iodylbenzoic acids, the respective sodium salts of 2- and 4-iodobenzoic acids should be used as the starting substrates, because mixtures containing the corresponding iodosyl derivatives as the main products along with the intended iodyl compounds are produced from the free parent acids.

A series of 20 pentamidine analogs were prepared using 2 general Schemes that evaluated heteroatoms, sulfobenzene and alkanediamide groups in the aliphatic linker and methoxy substituents attached to the benzene rings for efficacy against the fungal pathogen, Pneumocystis carinii in an ATP bioassay. All but one of the 20 bisamidines reduced the ATP content of the P. carinii over the 72 hr of the assay period. The highest activities were associated with the lack of methoxy groups and the presence of the O, N and S heteroatoms. Activity (IC50) for compounds 1, 5, 6, 10 ranged from 1.1 to 2.13 µM. The compound 11 with similar activity (1.33 µM), bears a sulfobenzene group at a nitrogen in the aliphatic linker. The alkanediamide-linked bisbenzamidines showed a moderate inhibition of ATP. Generally, the inclusion of a heteroatom in the aliphatic linker and absence of methoxy groups at the benzene rings were associated with higher activities in this assay. Of note, most of the compounds had little to no cytotoxicity in mammalian cell cultures. Although not quite as potent as other pentamidine derivatives, these compounds hold promise for decreased side effects within the mammalian host.

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Oxidative anion metatheses in the crude title iodides and chlorides produced the corresponding pure hydrogensulfates, nitrates, tetrafluoroborates, triflates, tosylates, as well as bromides and chlorides (only from the iodides) in 54—86% yields. These procedures are easier and shorter than earlier methods. By using modified oxidative metatheses in the title iodides (in the presence of HBr or HCl) it was possible either to isolate, or to detect only, the intermediate dihaloiodates(I), [Ar2I]+[IX2]− (X = Br or Cl). A complex Ph2I+Cl−·1/2I2 was also obtained in 56% yield. Tetraethylammonium iodide was similarly converted into pure tetrafluoroborate or dibromoiodate(I) in 75 and 76% yields, respectively.

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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-g-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.

The anti-protozoal drug pentamidine is active against opportunistic Pneumocystis pneumonia, but in addition has several other biological targets, including the NMDA receptor (NR). Here we describe the inhibitory potencies of 76 pentamidine analogs at 2 binding sites of the NR, the channel binding site labeled with [3H]MK-801 and the [3H]ifenprodil binding site. Most analogs acted weaker at the ifenprodil than at the channel site. The spermine-sensitivity of NR inhibition by the majority of the compounds was reminiscent of other long-chain dicationic NR blockers. The potency of the parent compound as NR blocker was increased by modifying the heteroatoms in the bridge connecting the 2 benzamidine moieties and also by integrating the bridge into a seven-membered ring. Docking of the 45 most spermine-sensitive bisbenzamidines to a recently described acidic interface between the N-terminal domains of GluN1 and GluN2B mediating polyamine stimulation of the NR revealed the domain contributed by GluN1 as the most relevant target.