Collect. Czech. Chem. Commun. 2004, 69, 833-849

Methylation of Acridin-9-ylthioureas. Structure, Fluorescence and Biological Properties of Products

Juraj Bernáta, Eva Balentováa, Pavol Kristiana,*, Ján Imricha, Erik Sedláka, Ivan Danihela, Stanislav Böhmb, Naďa Prónayovác, Kalevi Pihlajad and Karel D. Klikad

a Institute of Chemistry, Faculty of Science, P. J. Šafárik University, SK-041 67 Košice, Slovak Republic
b Department of Organic Chemistry, Institute of Chemical Technology, Prague, CZ-166 28 Prague 6, Czech Republic
c Faculty of Chemical and Food Technology, Central Laboratories, Slovak Technical University, SK-812 37 Bratislava, Slovak Republic
d Department of Chemistry, University of Turku, FIN-20014 Turku, Finland


The structure, fluorescence, biological properties and S(N)-methylation reactions of ten 1,1-alkyl/aryl-disubstituted 3-(acridin-9-yl)thioureas 4 have been studied. Various reaction conditions allowed to obtain corresponding S-methyl 5 and S,N-dimethyl derivatives 6 in good yields. Structure and stereochemistry of the synthesized products are demonstrated by ab initio quantum chemical calculations and NMR techniques including PDQF-COSY, selective INEPT and NOE-difference experiments. Remarkable upfield 13C shifts of resonance signals of carbons C-4a, C-10a adjacent to acridine N-10 are characteristic of hydroiodides in contrast to free bases. Z configuration in isothioureas 7 with secondary amino rest in relation to E configuration of isothioureas with primary amino rest is discussed. Of the obtained products, some isothiourea salts 6 exhibit more than 2 orders of magnitude higher intensity of fluorescence, using 9-isothiocyanatoacridine as a standard. The obtained isothiourea hydroiodides 5 and dimethylisothiourea iodides 6 show remarkable biological activity against Mycobacterium tuberculosis.

Keywords: Acridines; Isothioureas; Fluorescence; PDQF COSY; INEPT; NOE; DFT; Ab initio calculations; Antimycobacterial activity; NMR spectroscopy.

References: 21 live references.