Potential antitumor agents. 24. Synthesis and pharmacological behavior of imidazo[2,1-b]thiazole guanylhydrazones bearing at least one chlorine.

In connection with a previous research dealing with the antitumor activity of imidazo[2,1-b]-thiazole guanylhydrazones, this paper reports the synthesis of new derivatives which were tested for antitumor and positive inotropic activity. In most cases the cytotoxic data from the in vitro experiments (HeLa) were in agreement with the antitumor data in vivo (Ehrlich). The active compounds bear a phenyl ring at the 6 position. On the other hand, the most active cardiotonic agents were devoid of the phenyl ring.

Synthesis and cytotoxic activity of new peptides containing basic amino acid residues.

In search of more potent compounds endowed with a cytotoxic activity, a new series of basic peptides was synthesized using solid-phase methods. All peptides were purified by preparative reverse-phase HPLC and characterized by electrospray mass spectrometry. The cytotoxic activity was determined in cultured HeLa cells. The hexadecapeptides 5 and 6 showed a 50% inhibition at the concentration of 30 micrograms/ml. The salmina and the polyamino acids of L-arginine, L-histidine and L-lysine, containing sixteen residues, were virtually inactive. This demonstrates that a specific peptide sequence is necessary to obtain a positive response in HeLa test.

Enhancement of cytotoxic activity by synthesis of peptide multimeric forms.

Synthesis of four multimeric H-Lys-His-His-Arg-Lys-Lys-His-Arg-Lys-Arg-Lys-His-His-Lys-Arg-Lys-oH peptides containing two, four, eight and sixteen branches was carried out by solid phase utilizing a lysine core matrix. These multimeric peptides enhanced activity by inhibiting the colony-forming ability of HeLa cells, from twenty-four to fifty-six times in comparison with the monomeric form. Unexpectedly the peptide with only two-branched sequences showed the highest inhibitory activity.

Synthesis and cytotoxic activity of peptides containing basic amino acids residues.

We synthesized eight peptides containing from three to twenty residues of arginine, lysine and histidine, using an automated synthetiser and Fmoc strategy. All peptides were purified by preparative reverse-phase HPLC and characterized by electrospay mass spectometry. Cytotoxic activity was assessed on HeLa cells. One peptide inhibited the colony-forming ability of tumor cells.

Potential antitumor agents. 25 [1]. Synthesis and cytotoxic activity of 3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones.

The Knoevenagel reaction between 2-indolinones and 2-chloroindolaldehydes gave 3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones which were tested as potential antitumor agents on cultures of HeLa cells. 2-Chloro derivatives with at least one unsubstituted NH group, are promising candidates for further investigation.

Antitumor activity of an alkylating derivative of dipyridamole.

Synthesis of 2,6-Bis[bis(2-chloroethyl)amino]-4,8-dipiperidino-pyrimido [5,4-d]pyrimidine (DIP-C1) was carried out, and the new derivative showed cytotoxic activity comparable to other alkylating drugs on cultured P388 leukaemia cells and HeLa cells. The present paper reports the effects of DIP-C1 on respiration of Ehrlich ascites tumor cells and on survival of the mice implanted with Ehrlich ascites tumor cells. The compound showed a significant activity in both experimental models.

Potential coanthracyclinic activity of pyridylmethylene-2-indolinones.

The paper reports the cytotoxic activity of pyridylmethylene-2-indolinones previously described as cardiotonics and the synthesis of three analogs of the most potent cytotoxic agent. Some of these compounds could be useful, when associated with anthracyclines, to reduce the cardiotoxicity of these potent antitumor drugs.

Potential antitumor agents. XXII. Synthesis and cytotoxic activity of imidazo [2,1-b]thiazole adamantylthioureas.

A series of imidazo[2,1-b]thiazole adamantylthioureas (3a-f) was synthesized by reaction of the methylsulfanylethylamines 2a-f (prepared in turn from the hydroxymethylimidazo[2,1-b]thiazoles 1a-f and cysteamine) with 1-adamantylisothiocyanate. 1-Adamant-1-yl-3-[2-(6-chloro-2,3- dihydroimidazo[2,1-b]thiazol-5-ylmethylsulfanyl)ethyl] thiourea (3d) was significantly active.

Potential antitumor agents XIX [1]. Synthesis and antitumor activity of tricyclic compounds related to lotifazole.

The synthesis of phenothiazine and anthraquinone derivatives, bearing at least one fragment present in lotifazole, is reported. Some of the new compounds showed antitumor activity in vitro (P388 leukemia cells) and in vivo (Ehrlich ascites tumor cells in mice).

Potential antitumor agents. XX (1). 6-Anilinoimidazo[2,1-b]thiazoles.

The synthesis of 6-anilinoimidazo[2,1-b]thiazoles, related to the well-known antitumor agent amsacrine, is reported. The cytotoxic activity of the new compounds was evaluated on HeLa cells. Compound 3a, the most closely related to amsacrine, was significantly active.