[Synthesis and in vivo antitumor effect of N,N-di(2-chlorethyl) hydrazides of natural alpha-aminocarboxylic acids]. / Synthese und geschwulsthemmende Wirkung in vivo von N,N-Di(2-chlorethyl)hydraziden natürlicher alpha-Aminocarbonsäuren.

N,N-Di(2-chlorethyl)hydrazides of the following alpha-amino-carboxylic acids were synthesized: glycine, valine, norvaline, lysine, phenylalanine, tyrosine, cystine, homocystine, aspartic and glutamic acid as well as the N,N-diethylhydrazides of glycine, phenylalanine and cystine. The N,N-di-(2-chlorethyl)hydrazides have a pronounced effect on solid tumours (tumour growth inhibition by 30-100%), whereas their inhibition activity with ascite tumours is negligible. N,N-diethylhydrazides show analogous but less expressed biological effect.

[Synthesis and antitumor action of N,N-di(2-chlorethyl)-hydrazines of alpha-aminocarboxylic acid antimetabolites]. / Synthese und geschwulsthemmende Wirkung von N,N-Di(2-chlorethyl)-hydrazinen der alpha-Aminocarbonsäureantimetabolite.

The N,N-di(2-chlorethyl)hydrazides of the following alpha-aminocarboxylic acid antimetabolites: methioninsulphoxide, ethionine, 2-, 3- and 4-fluorophenylalanine, 4-nitrophenylalanine and 2,2-dimethyl-thiazolidine-4-carboxylic acid were synthesized. Preliminary studies of the activity on experimental tumour models were carried out. It was shown that these compounds have a high antitumour effect (80-100%) on sarcoma Yoshida and carcinosarcoma Walker.

Antibacterial and antitumor activity of platinum complexes of hydrazinopyrimidines and amidrazones.

Antibacterial and antitumor activity of 10 platinum complexes of N3-phenylsubstituted amidrazones and hydrazinopyrimidines has been studied. It has been found that the platinum complexes of amidrazones, containing substituents in the benzene nuclear or in the NH2-group, exhibit a better antibacterial activity while those without substituents in their benzene nuclears have a pronounced antibacterial activity mostly on bacterial test-systems used in the prescreening of antitumor agents (S. lutea and UV-2). Most of the studid platinum complexes of hydrazinopyrimidines show inhibitory effect on the bacterial strains used in the prescreening of antitumor agents. The antitumor activity of platinum complexes has been tested on L1210 leukemia, adenocarcinoma 755 and Lewis carcinoma. An inhibitory effect is observed in the case of adenocarcinoma 755 with the cis-isomer of the platinum complex of N3-p-tolylbenzamidrazone (the tumor growth was 60% suppressed).

Studies on the antimycotic activity of 5-fluoroorotic acid.

The antimycotic effect of 5-fluoroorotic acid (FOA) was studied in experimental and clinical conditions. The experiments in vitro were performed on 21 strains of fungi isolated mainly from clinical material. The effect of FOA was compared with those of the structurally related drug 5-fluorocytosine. The clinical study was performed on 40 patients aged 18 to 75 years with mycological diseases. FOA in different dosage forms was applied topically 2 to 3 times daily for 30 days. Microscopic and cultured mycological studies were performed before and after treatment. The results showed that FOA possesses a well-expressed anticandidal effect close to that of 5-fluorocytosine, as well as moderate antidermatophytal effects. Clinical studies of 1% FOA cream showed good therapeutic effects similar to that of Ung. Whitfield, but 55% of the patients developed relapse of the lesions after discontinuation of the treatment. Higher concentrations of FOA included in milk suspension and powder induced severe side effects of local irritability.

Biological activity and mode of action of some dihydroorotic and dihydroazaorotic acid derivatives.

The conversion of six dihydroorotate analogues by the dihydroorotate dehydrogenase (DHO-DH) of plant and animal mitochondria was studied. In the case of plant DHO-DH the dehydrogenation of analogues was as follows: Dihydroorotic acid (DHO) (control, 100%), DHO-hydrazide (40%), azaDHO (13%), azaDHO-ethyl ester (23%), azaDHO-hydrazide (11%), dihydrouracil (0%), dihydrothymine (0%). When animal DHO-DH was used the analogues were practically not dehydrogenated. These compounds were also tested as inhibitors of DHO-dehydrogenation. AzaDHO, azaDHO-hydrazide and azaDHO-ethylester inhibited this reaction by 75, 70% and 60%, respectively, for plant DHO-DH. AzaDHO and azaDHO-ethylester inhibited this reaction to 90% and 70%, respectively, for animal enzyme. The other analogues had no effect. The compounds showed a moderate antibacterial activity. AzaDHO was more active than azaDHO-ethyl ester and azaDHO-hydrazide. A considerable inhibitory effect of azaDHO and azaDHO-ethyl ester was observed on the growth of St. aureus mutant UV-2 and S. lutea. The analogues were little active against the experimental mouse tumors leukemia L 1210, Lewis lung carcinoma (LLC) and B-16 melanoma. AzaDHO-ethyl ester and azaDHO-hydrazide inhibited the growth of LLC by 59% and 56%, respectively. In addition, the effect of analogues on the growth of plant cells was studied. AzaDHO and azaDHO-ethyl ester inhibited the growth of tomato cells in suspension culture by 10% and 41%, respectively.

Inhibitory effects of pyruvic acid semi- and thiosemicarbazones on the growth of bacteria, yeasts, experimental tumours and plant cells.

Pyruvic acid semi- and thiosemicarbazones (1 and 2, respectively) were tested as inhibitors of bacterial, fungal, experimental tumour and plant cell growth. 1 and 2 displayed a growth-inhibitory effect in vitro against different bacterial strains, and especially against St. aureus mutant UV-2 and S. lutea. The compounds proved to have low activity in vivo against L 1210 and P 388 leukemia, adenocarcinoma 755 and melanoma B 16. 2 inhibited strongly the growth of cultured cells of Lycopersicon esculentum (100% inhibition at a concentration of 1,5 mumol/ml) while 1 was not active.

[Synthesis and antibacterial and antitumoral activity of some methylhydrazonium salts of pyrimidine bases and their analogues (author's transl)]. / Synthese, antibakterielle und geschwulsthemmende Wirkung einiger Methylhydrazoniumsalze von Pyrimidinbasen und deren Analoga.

On reacting pyrimidine metabolites containing a carboxyl or sulfhydryl group with methylhydrazine or N-benzyl-N'-methylhydrazine, various methylhydrazonium salts of these metabolites were synthetized, e.g., the salts of 5-fluororotic acid, 5-azaorotic acid, 2-thiouracil-5-carboxylic acid and 2-thio-6-azathymine. Some of these salts exhibited a more marked antibacterial activity against St. aureus and several of its mutants as well as a greater antitumoral activity against different transplantable tumours than their single components.

Antiviral, antibacterial and antitumor activity of the hydrazide and the ethyl ester of 2,2'-anhydro-1-(beta-D-arabinofuranosyl)-orotic acid.

It has been demonstrated that the hydrazide and the ethyl ester of 2,2'-anhydro-1-(beta-D-arabinofuranosyl) orotic acid inhibit selectively the multiplication of some DNA-containing viruses (PsRV, VV, AdV5), suppress the growth of E. coli and St. aureus in vitro and exhibit an antitumor effect with Lewis lung carcinoma and sarcoma 298.

[The antibacterial activity of some substituted cysteine sulphonamides and peptides containing cysteine sulphonamide]. / Antibakterielle Aktivität einiger substituierter Cysteinsulfonamide und cysteinsulfonamidhaltiger Peptide.

The authors investigated the antibacterial activity of some cysteine sulphonamides substituted in the sulphonamide group as well as that of some peptides containing cysteine sulphonamide. They found that the antibacterial activity of these compounds was in part considerably stronger than that of cysteine sulphonamide.

A new substance effective against transplantable tumors in vivo: L-cystine-bis-(N,N-beta-chloroethyl)-hydrazide.

It is shown that L-cystine-bis-(N,N-beta-chloroethyl)-hydrazide-hydro-bromide possesses strong (50-100%) inhibitory effect in vivo against myeloma P-8, carcinosarcoma Walker, lymphosarcoma Pliss, sarcoma Yoshida, sarcoma Jensen and sarcoma 180 in doses 5-12 mg/kg/day. No suppression of the growth of Ehrlich ascites tumor was observed. The acute toxicity (LD50) of this substance on mice and rats is 71 mg/kg and 47 mg/kg respectively.

Antibacterial and antitumor activity of some derivatives of ureidosuccinic acid.

The effect of several derivatives of ureidosuccinic acid on the growth of Escherichia coli 387, Staphylococcus aureus strain 209 and its mutant UV-2, Sarcina lutea, Candida tropicalis and Neurospora crossa 9863 as pre-screening systems for antitumor activity was studied. It was found that dihydrazide of D,L-ureidosuccinic acid (DHUA) had a marked antibacterial activity. The inhibitory effect of DHUA on N. crassa could not be removed by aspartic acid, ureidosuccinic acid, dihydroorotic acid, orotic acid, uracil or cytosine. DHUA suppressed the growth of Myeloma P-8 by 38%, that of Sarcoma 180 by 12% and that of Yoshida sarcoma by 19%. No effect was found on the growth of Lymphosarcoma Pliss.