Cytotoxic, antiviral (in-vitro and in-vivo), immunomodulatory activity and influence on mitotic divisions of three taxol derivatives: 10-deacetyl-baccatin III, methyl (N-benzoyl-(2'R,3'S)-3'-phenylisoserinate) and N-benzoyl-(2'R,3'S)-3'-phenylisoserine.
The aim of this study was to evaluate cytotoxic, antiviral (in-vitro and in-vivo) and immunomodulatory activity, as well as the influence on mitotic division, of three taxol derivatives representing modified parts of its molecule: 10-deacetyl-baccatin III, methyl (N-benzoyl-(2'R,3'S)-3'-phenylisoserinate) and N-benzoyl(2'R,3'S)-3'-phenylisoserine. The cytotoxicity of the compounds, assessed by the formazane method, was relatively low, with a 50% cytotoxic concentration (CC50)>500 microg mL-1. Moreover, all tested compounds inhibited Herpes simplex type 1 virus (HSV-1) replication in non-cytotoxic concentrations in-vitro. Selectivity indices were in the range 9.5-46.7. Anti-HSV-1 activity of the compounds may be associated with their influence on mitotic division. All of the compounds decreased the number of cell divisions. Mitotic indices ranged from 40/1000 (4.0%) to 62/1000 (6.2%). One compound, 10-deacetyl-baccatin III, influenced the growth of tumours induced in mice by infection with Moloney murine sarcoma virus. The effect of the tested compounds on T lymphocyte proliferation was evaluated by measurement of the activity of tritiated thymidine incorporated into DNA of dividing cells. One compound, methyl (N-benzoyl-(2'R,3'S)-3'-phenylisoserinate), inhibited T lymphocyte proliferation. This paper demonstrates that modified parts of the taxol molecule possess various types of biological activity in-vitro and in-vivo. Further experiments, focused on revealing their mechanisms of action, are necessary.
Krawczyk
Ewa
E
Chair and Department of Medical Microbiology, Medical University of Warsaw, 5 Chalubinski St, 02-004 Warsaw, Poland. ewakrawczyk@gazeta.pl
Luczak
Mirosław
M
Kniotek
Monika
M
Nowaczyk
Maria
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D008980:Moloney murine sarcoma virus / Q000187:drug effects; D012694:Serine / Q000031:analogs & derivatives / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology*; D014709:Vero Cells
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001549:Benzamides; C504232:N-benzoyl-3'-phenylisoserine; D043823:Taxoids; C504231:methyl (N-benzoyl-3'-phenylisoserinate); D012694:Serine; C042213:10-deacetylbaccatine III