Effects of some antineoplastic drugs (vincristine, doxorubicin and epirubicin) on human platelet aggregation.

The effects of some antineoplastic drugs (vincristine, doxorubicin and epirubicin) on collagen- and ADP-induced human platelet aggregation are investigated. Platelet rich plasma (PRP) and platelet poor plasma (PPP) from healthy male and female donors were used. The PRP was adjusted with analogous PPP to 300,000 platelets/microliters. Platelet aggregation was studied according to Born's turbidimetric technique using an Aggrecorder II PA 3220 with collagen at a concentration of 10 micrograms/ml and ADP at a concentration of 30 microM. Vincristine, doxorubicin and epirubicin significantly (p < 0.01) inhibited collagen- and ADP-induced platelet aggregation. The vincristine induced inhibition was higher than that induced by doxorubicin or epirubicin. The effects of doxorubicin and epirubicin were more intense on ADP-induced platelet aggregation than on the collagen induced one. Moreover, the doxorubicin inhibition of ADP-induced platelet aggregation was greater than the epirubicin one. In conclusion, our study shows that vincristine, doxorubicin and epirubicin inhibit human platelet aggregation. The present results may improve the therapeutic use of these drugs since it has been clearly shown that drugs with antiplatelet activity could block metastases.

2H-1-benzopyran derivatives with platelet antiaggregating and other activities.

The synthesis of some N,N-disubstituted 4-amino-5,6,7,8-tetrahydro-3,6- diphenyl-2H-1-benzopyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 2-aminomethylene-4-phenylcyclohexanones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid and an appreciable antiarrhythmic activity, as well as weak anti-inflammatory and local anesthetic activities in rats and mice.

N-substituted 4-carboxy-1-phenyl-1H-pyrazole-5-propanamides with antiinflammatory, analgesic, antipyretic and platelet antiaggregating activities.

The synthesis of a series of N-substituted 4-carboxy-1-phenyl-1H-pyrazole-5-propanamides by reaction of 1-phenyl-1H-oxepino[4,3-c]pyrazole-4(8H),6(7H)-dione with aromatic primary amines is described. Some amides showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as moderate antiinflammatory, analgesic and antipyretic activities in rats or mice.

N-acyl-4,7,7-trimethyl-N-phenyl-3-(1-piperidinyl or dimethylamino)bicyclo[2.2.1]hept-2-ene-2-carbothioamides with platelet antiaggregating and other activities.

A series of N-acyl-4,7,7-trimethyl-N-phenyl-3-(1-piperidinyl or dimethylamino)bicyclo[2.2.1]hept-2-ene-2-carbothioamides was prepared in excellent yields by reaction of 4,7,7-trimethyl-N-phenyl-3-(1-piperidinyl or dimethylamino)bicyclo[2.2.1]hept-2-ene-2-carbothioamides with a number of aromatic or heterocyclic acyl chlorides in dry pyridine solution and in the presence of sodium hydride. Some of the above compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid; moreover, some compounds exhibited moderate analgesic, antiinflammatory and hypotensive activities in mice or rats.

3,5-Diphenyl-1H-pyrazole derivatives. X. N-substituted 1-(2-aminopropyl)- and 1-(3-amino-2-hydroxypropyl)-3,5-diphenyl-1H-pyrazoles with antiinflammatory and other activities.

The syntheses of 1-(2-hydroxypropyl)-3,5-diphenyl-1H-pyrazole 1 by reaction of 1-hydrazino-2-propanol with dibenzoylmethane and of N-substituted 1-(2-aminopropyl)-3,5-diphenyl-1H-pyrazoles 3 by reaction of primary and secondary amines with the tosylate of 1, as well as of N-substituted 1-(3-amino-2-hydroxypropyl)-3,5-diphenyl-1H-pyrazoles 6 starting from 3,5-diphenyl-1H-pyrazole, are described. Some compounds 3 and 6 showed remarkable antiinflammatory activity in rats, as well as weak analgesic, antipyretic, antiarrhythmic, hypotensive activities in mice and rats and moderate platelet antiaggregating effects in vitro.

Cyclohepta[b]pyran derivatives with platelet antiaggregating and other activities.

The synthesis of some N,N-disubstituted 4-amino-6,7,8,9-tetrahydro-3-phenylcyclohepta[b]pyran-2(5H)-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 2-aminomethylenecycloheptanones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as weak local anesthetic, antiinflammatory and analgesic activities in mice and rats.

Effects of tetanus toxin, Salmonella typhimurium porin, and bacterial lipopolysaccharide on platelet aggregation.

Endotoxins may interfere with platelet aggregation by interacting with the platelet membrane. The aim of this study was to evaluate the effects of tetanus toxin, Salmonella typhimurium porin, and bacterial lipopolysaccharide (LPS) on platelet aggregation induced by ADP and thrombin in vitro. Spontaneous platelet aggregation and platelet aggregation induced by ADP and thrombin were measured. Our results show that Salmonella typhimurium porin and bacterial LPS enhanced human and rabbit platelet aggregation induced by ADP and thrombin. Tetanus toxin did not affect platelet aggregation.

Esters of 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-endo-ol with antiarrhythmic and other activities.

The synthesis of esters derived from 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-endo-ol, obtained by LiAlH4 reduction of 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-one, is described. Some of these esters showed an appreciable antiarrhythmic activity in rats, as well as moderate hypotensive and local anesthetic activities in rats and mice, respectively.

2H,5H-[1]benzothiopyrano [4,3-b]pyran derivatives with platelet antiaggregating activity.

The synthesis of some N,N-disubstituted 4-amino-3-phenyl-2H,5H-[1]benzothiopyrano [4,3-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 3-aminomethylene-2,3-dihydro-4H-1-benzothiopyran-4-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a strong platelet antiaggregating activity in vitro, superior to that of acetylsalicylic acid.