1- Formylisoquinoline thiosemicarbazone

Complexes of 2-formylquinoline and 1-formylisoquinoline thiosemicarbazones, 20 and 21, respectively, have been prepared, but iron(III) complexes were not included in the initial study [147], More recently [132], an iron(III) complex of 1-formylisoquinoline thiosemicarbazone, [Fe(21)Cl3] has been found to have a magnetic moment of about 2.1, g of 2.146, and involve the neutral ligand bound in a tridentate manner. A complex of the same stoichiometry was reported for 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, 22. Its magnetic moment is about 2.1 and g, = 2.126. 

Iron(II) complexes of general formula [FeLA2] A = Cl, Br, I, NO3, NCS or NCSe have been formed [145] with both 2-formylquinohne thiosemicarbazone, 20, and 1-formylisoquinoline thiosemicarbazone, 21. All are characterized as five-coordinate, high spin iron(II) complexes and the electronic spectra are assigned consistent with distorted trigonal bipyramidal structures. 

Ethanol-dimethoxypropane solutions of either 1-formylisoquinoline or 2-formylquinoline thiosemicarbazone and cobalt(II) salts yield [Co(L)A2] complexes where A = Cl, Br, I, NO3, NCS, or NCSe [147]. All are non-electrolytes, have magnetic moments of 4.30-4.70 B.M. and are five coordinate with approximate trigonal bipyramidal stereochemistry involving NNS coordination based on electronic and infrared spectra. [Co(21-H)2] 2H2O was isolated from a cold methanolic solution of cobalt(II) chloride and 1-formylisoquinoline thiosemicarbazone [187]. Infrared spectral studies show NNS coordination the electronic spectral bands fit a distorted octahedral symmetry, and the magnetic moment is 4.48 B.M. 

More recently [147], five-coordinate, paramagnetic complexes of stoichiometry [NiLAj] (A = Cl, Br, I, NO3, NCS, and NCSe) have been prepared from both 2-formylquinoline and 1-formylisoquinoline thiosemicarbazone, 20 and 21, respectively. Bonding of the neutral ligands is considered to be NNS. 

Although 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, 22, also forms [Ni(22)Cl2] with chemical properties similar to [Ni(21)Cl2], it, along with other metal complexes of 22, showed no activity against P388 lymphocytic leukemia test system in mice [202]. 

French and Blanz [9-13] extended these observations by testing a series of formyl heteroaromatic thiosemicarbazones for anticancer activity several of these derivatives, especially 1-formylisoquinoline thiosemicarbazone [10], 2-formyl-3-hydroxypyridine thiosemicarbazone [11] and 2-formyl-5-hydroxy-pyridine thiosemicarbazone [13] showed significant tumour-inhibitory activity when tested against a spectrum of transplanted murine neoplasms. 

Studies conducted on the inhibition of libonucleoside diphosphate reductase by the preformed iron chelate of 1-formylisoquinoline thiosemicarbazone (1) [(Fe)IQ-11 have shown that under appropriate conditions (Fe)IQ-1 was essentially equal to (1) as an inhibitor of enzymatic activity (78). At a concentration of (Fe)IQ-l which inhibited enzymatic activity by 73% in the absence of added Fe, only 30% inhibition was observed when Fe " was added to the preparation. In contrast, (1) decreased enzyme activity 65% in the presence of Fe but only 15% without Fe. The findings imply that Fe(IQ-l) is the active form of the inhibitor and stress further complexities in the mode of inhibition. 

Twenty percent of the radioactivity from (1) labelled in the side-chain was excreted in the urine of mice and 2.8% in the faeces in 16 h [35]. During an 8-h period, about 2% of the radioactivity was present in the respiratory CO2 when side-chain labelled (3 - C), but not ring labelled (1- C) 1-formylisoquinoline thiosemicarbazone, was administered. Furthermore, these workers found that the half-life of radioactivity from (1) in the blood of dogs was about 4 h, and... 

The first systematic approach to evaluate the effects of various substituents on the heterocyclic ring on the biological activity of these agents was undertaken by Agrawal, Booth and Sartorelli [34]. The candidate deemed most appropriate for such a study was 1-formylisoquinoline thiosemicarbazone (1), since it was extensively employed in biochemical studies as the model agent of the series and had been shown to cause pronounced inhibition of the growth of a relatively... 

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