Crystal and molecular structure and in vitro antiproliferative and antitumor activity of two organotin (IV) carbohydrate compounds.
3-C-[(Triphenylstannyl)methyl]-1,2:5,6-di-O-isopropylidene-alpha-D -allofuranose (Ph3SnCH2 carbohydrate) and 3-C-(triphenylstannyl)-1,2:5,6-di-O-isopropylidene-alpha-D-allo furanose (Ph3Sn carbohydrate) were studied by diffraction methods, space groups P2(1)2(1)2(1), a = 6.073 (1), b = 13.091 (3), c = 37.739 (13) and a = 8.3219 (9), b = 11.876 (1), c = 29.575 (5) A, respectively; both compounds have distorted tetrahedral coordination. The biological study of these compounds along with Ph3SnCl shows the following: (a) With respect to their capacity to interfere with DNA, RNA, and protein synthesis of isolated fastly proliferating thymocytes, the triphenyltin carbohydrates are less active than Ph3SnCl. Protein synthesis was found to be most sensitive with an IC50 value of approximately 0.3 microM for Ph3SnCl, 3 microM for Ph3Sn-carbohydrate, and greater than 5 microM for Ph3SnCH2-carbohydrate; (b) The in vitro activity toward the mouse tumor cell lines MOPC315, P815, SL2, and L1210, which was also performed for Bu2SnCl2, also showed that the two triphenyltin carbohydrates were less effective than Ph3SnCl. From these results it is concluded that in vitro these Sn-C bonded triphenyltin carbohydrates are less active than Ph3SnCl. Ph3Sn carbohydrate is more active than Ph3SnCH2 carbohydrate, and this may be related with the long Sn-C (of the carbohydrate moiety) bond distance (2.225 (8) A) for the former compound. This compound shows a biological activity which is in contrast to the normal inactivity of tetraorganotins and is the first active member of this family whose molecular structure is reported.
Caruso
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F
Istituto di Strutturistica Chimica 'G. Giacomello', CNR, CP10, Rome, Italy.
Bol-Schoenmakers
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M
Penninks
A H
AH
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D003460:Crystallization; D004247:DNA / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008958:Models, Molecular; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009947:Organotin Compounds / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009947:Organotin Compounds; C081105:3-C-((triphenylstannyl)methyl)-1,2-5,6-di-O-isopropylidene-D-allofuranose; C081106:3-C-(triphenylstannyl)-1,2-5,6-di-O-isopropylidene-D-allofuranose; D012313:RNA; D004247:DNA