The Carcinostatic Activity of Thiosemicarbazones of Formyl Heteroaromatic Compounds.¹ III. Primary Correlation

Abstract

Thiosemicarbazciiies of 41 formyl heterocycles and two heterocyclic ketones were prepared and tested on four mouse tumor systems. The variables studied included: 16 ring systems, different positions of attachment of the formyl group relative to the ring heteroatoms, additional ring substituents, and terminal substituents in the thiosemicarbazone side chain. The minimum requirement for act,ivity is formyl group attachment to a ring carbon CY to an uneiicumbered ring nitrogen of heteroaromatic character. The T-electron density milst be low at this ring carbon and fairly high at the ring nitrogen. All the active compounds are potent ligands for the transition metals from iron through zinc. The aiititiimor activities of the thiosemicarbaaones of 1-formylisoquirioline and 3-hydroxy-2-formylpyridine are siifficiently good to merit extensive further study.

Structure of a carcinogenic agent: 1-formyl-3-thiosemicarbazide

“…(Nandi, Chaudhuri, Mazumdar & Ghosh, 1984a,b;Cavalca, Nardelli & Fava, 1962). These compounds have exhibited antibacterial, antiviral, carcinostatic or carcinogenic activities (Johnson, Joyner & Perry, 1952;French & Blanz, 1965Williams, 1972;Erturk, Morris, Cohen, Von Esch, Crovetti, Price & Bryan, 1971;Jensen & Jensen, 1952). It has been suggested that the biological activities of these compounds are due to their capability to form metal complexes (Kirschner, Wei, Francis & Bergrnan, 1966;Palenik, Rendle & Carter, 1974).…”

Structure of 4-(4-methoxyphenyl)thiosemicarbazide

“…The antibacterial, antiviral and anticancer activities possessed by substituted thiosemicarbazides and thiosemicarbazones have generated rapidly growing interest in the chemical, biochemical and structural aspects of these compounds (Johnson, Joyner & Perry, 1952;French & Blanz, 1966;Agrawal, Booth & Sartorelli, 1968;Agrawal, Cushley, McMurray & Sartorelli, 1970;Williams, 1972;Agrawal, Booth & Sartorelli, 1973;Kuroda, Neidle & Wilman, 1984). It has been suggested that the biological activities of these groups of N,S donor ligands originate from their metal-chelating and reductive capacities (Kirschner, Wei, Francis & Bergman, 1966;Palenik, Rendle & Carter, 1974).…”

The crystal and molecular structures of thiosemicarbazones; an antitumor agent 5-hydroxy-2-formylpyridine thiosemicarbazone sesquihydrate and the inactive acetone thiosemicarbazone

“…For example, acetone thiosemicarbazone (ATSC) has no known biological activity while Hagenbach & Gysin (1952) reported that 4-formylpyridine thiosemicarbazone has some antitubercular activity. French & Blanz (1966) found that e-(N)-formyl heteroaromatic thiosemicarbazones have antitumor activity but their toxicity has limited their clinical usefulness. However, Blanz & French (1968) found that 5-hydroxy-2-formylpyridine thiosemicarbazone, henceforth 5-OH-2FPTSC, had a much lower toxicity while still retaining favorable antitumor activity.…”