Reaction(s) of -guanosine monophosphate ( GMP) with di- and triorganotin(IV) chloride(s) led to formation of organotin(IV) derivatives of general formulae, [R2Sn( -GMP)·H2O]n and [(R′3Sn)2( -GMP)·H2O]n, where R？=？Me, n-Bu, and Ph; R′？=？Me, i-Pr, n-Bu, and Ph; ( -GMP)2？ = -guanosine monophosphate. An attempt has been made to prove the structures of the resulting derivatives on the basis of FT-IR, multinuclear 1H, 13C, and 119Sn NMR and 119Sn M？ssbauer spectroscopic studies. These investigations suggest that both di- and triorganotin(IV)- -guanosine monophosphates are polymeric in which ( -GMP)2？ is bonded through phosphate group resulting in a distorted trigonal bipyramidal geometry around tin. The ribose conformation in all of the derivatives is C3′-endo, except diphenyltin(IV) and tri-i-propyltin(IV) derivatives where it is C2′-endo. All of the studied derivatives exhibited mild-to-moderate anti-inflammatory activity (~15.64–20.63% inhibition) at 40？mg？kg？1 dose and LD50 values >？400？mg？kg？1 in albino rats. 1. Introduction The field of cancer chemotherapy has been developed enormously during the past fifty years. Prior to 1969, however, the arsenal of chemotherapeutic agents was devoid of compounds which are inorganic in nature because of generally accepted belief that most metals and their compounds were potentially carcinogenic [1]. In 1969, Rosenberg and his coworkers made the serendipitous discovery [2] that certain Pt compounds were potent antitumor agents against Sarcoma 180 tumors and L1210 leukemia in mice and must be considered to be an outstanding development in the field of metal compounds in medicine [3]. Cis-platin is the first drug from inorganic chemistry to have come under routine clinical use in medical oncology [3]; in 1986, it was the largest selling anticancer drug worldwide. Its success placed the co-ordination chemists on the front line in the fight against cancer and stimulated the search for other metal-containing compounds with potential anticancer activity. In last 20 years about more than 12000 complexes of 55 metals have been tested [4], many of them are now entering for clinical trials, and some may ultimately rival cis-platin [5–7]. Although the majority of these successes involved complexes containing transition metal ions such as Cr, Co, Cu, Pd, Rh, Ru, and Au [5–8], but some main group metals (i.e., Al, Ga, In, ad Tl; Ge, Sn, and Pb; Bi and Po) compounds [1], especially organotins, have also been discovered which show promise as future members of man’s anticancer arsenal [9–13]. Further, several organotin(IV)
References
[1]
S. G. Ward and R. C. Taylor, “Anti-tumor activity of the main-group elements: aluminum, gallium, indium, thallium, germanium, lead, antimony and bismuth,” in Metal-Based Anti-Tumor Drugs, M. F. Gielen, Ed., pp. 1–54, Freund Publishing House, London, UK, 1988.
[2]
B. Rosenberg, L. VanCamp, J. E. Trosko, and V. H. Mansour, “Platinum compounds: a new class of potent antitumour agents,” Nature, vol. 222, no. 5191, pp. 385–386, 1969.
[3]
B. Rosenb, “Cis-platin: its history and possible mechanisms of action,” in Cis-Platin-Current Status and New Developments, A. W. Prestayko, S. T. Crooke, and S. K. Carter, Eds., pp. 9–20, Academic Press, New York, NY, USA, 1980.
[4]
P. M. May and R. A. Bulman, “The present status of chelating agents in medicine,” Progress in Medicinal Chemistry, vol. 20, pp. 225–336, 1983.
[5]
P. K？pf-Maier and H. K？pf, “Non-platinum-group metal antitumor agents: history, current status, and perspectives,” Chemical Reviews, vol. 87, no. 5, pp. 1137–1152, 1987.
[6]
B. K. Keppler, C. Friesen, H. G. Moritz, H. Vongerichten, and E. Vogel, “Tumorinhibiting bis(β-diketonato) metal complexes. Budotitane, cis-diethoxybis(1- phenylbutane-1,3-dionato)titanium(IV); The first transition metal complex after platinum to qualify for clinical trials,” Structure and Bonding, vol. 78, pp. 97–127, 1991.
[7]
S. Fruhauf and W. J. Zeller, “In vitro evaluation of platinum, titanium and ruthenium metal complexes in cisplatin-sensitive and -resistant rat ovarian tumors,” Cancer Chemotherapy and Pharmacology, vol. 27, no. 4, pp. 301–307, 1991.
[8]
G. Sava, S. Zorzet, and T. Giraldi, “Antineoplastic activity and toxicity of an organometallic complex of ruthenium(II) in comparison with cis-PDD in mice bearing solid malignant neoplasms,” European Journal of Cancer and Clinical Oncology, vol. 20, no. 6, pp. 841–847, 1984.
[9]
C. Pettinari and F. Marchetti, “Chemical and biotechnological developments in organotin cancer chemotherapy,” in Tin Chemistry, Fundamentals, Frontiers, and Applications, A. G. Davies, M. Gielen, K. H. Pannell, and E. R. T. Tiekink, Eds., pp. 454–468, John Wiley & Sons, New York, NY, USA, 2008.
[10]
A. K. Saxena and F. Huber, “Organotin compounds and cancer chemotherapy,” Coordination Chemistry Reviews, vol. 95, no. 1, pp. 109–123, 1989.
[11]
M. Gielen, P. Lelieveld, D. de Vos, and R. Willem, “In vitro antitumor activity of organotin compounds,” in Metal-Based Antitumor Drugs, M. Gielen, Ed., pp. 29–54, Freund Publishing House, London, UK, 1992.
[12]
M. J. Clarke, F. Zhu, and D. R. Frasca, “Non-platinum chemotherapeutic metallopharmaceuticals,” Chemical Reviews, vol. 99, no. 9, pp. 2511–2533, 1999.
[13]
M. Nath, S. Pokharia, and R. Yadav, “Organotin(IV) complexes of amino acids and peptides,” Coordination Chemistry Reviews, vol. 215, no. 1, pp. 99–149, 2001.
[14]
M. Nath, S. Pokharia, G. Eng, X. Song, and A. Kumar, “Comparative study of structure-activity relationship of di- and tri- organotin(IV) derivatives of amino acid and peptides,” Journal of Organometallic Chemistry, vol. 669, no. 1-2, pp. 109–123, 2003.
[15]
M. Nath, S. Pokharia, G. Eng, X. Song, and A. Kumar, “Diorganotin(IV) derivatives of dipeptides containing at least one essential amino acid residue: synthesis, characteristic spectral data, cardiovascular, and anti-inflammatory activities,” Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, vol. 34, no. 10, pp. 1689–1708, 2004.
[16]
M. Nath, R. Jairath, G. Eng, X. Song, and A. Kumar, “Interaction of triorganotin(IV) cations with pyrimidine bases/nucleoside: synthesis, spectral characterization and biological studies of a novel triphenyltin(IV) derivative of thymidine,” Inorganic Chemistry Communications, vol. 7, no. 10, pp. 1161–1163, 2004.
[17]
M. Nath, S. Pokharia, G. Eng et al., “New trimethyltin(IV) derivatives of dipeptides: synthesis, characteristic spectral studies and biological activity,” Applied Organometallic Chemistry, vol. 18, no. 9, pp. 460–470, 2004.
[18]
M. Nath, S. Pokharia, G. Eng, X. Song, and A. Kumar, “New triorganotin(IV) derivatives of dipeptides as anti-inflammatory- antimicrobial agents,” European Journal of Medicinal Chemistry, vol. 40, no. 3, pp. 289–298, 2005.
[19]
M. Nath, S. Pokharia, G. Eng, X. Song, and A. Kumar, “New triorganotin (IV) derivatives of dipeptides as models for metal-protein interactions: synthesis, structural characterization and biological studies,” Spectrochimica Acta—Part A, vol. 63, no. 1, pp. 66–75, 2006.
[20]
M. Nath, H. Singh, P. Kumar, A. Kumar, X. Song, and G. Eng, “Organotin(IV) tryptophanylglycinates: potential non-steroidal anti inflammatory agents; crystal structure of dibutyltin(IV) tryptophanylglycinate,” Applied Organometallic Chemistry, vol. 23, no. 9, pp. 347–358, 2009.
[21]
M. Nath, H. Singh, G. Eng, X. Song, and A. Kumar, “Syntheses, characterization and biological activity of diorganotin(IV) derivatives of 2-amino-6-hydroxypurine (guanine),” Inorganic Chemistry Communications, vol. 12, no. 10, pp. 1049–1052, 2009.
[22]
M. Nath, H. Singh, G. Eng, and X. Song, “Interaction of organotin(IV) moieties with nucleic acid constituent: synthesis, structural characterization and anti-inflammatory activity of tri-i-propyltin(IV) and diorganotin(IV) derivatives of guanosine,” Inorganic Chemistry Communications, vol. 14, no. 9, pp. 1381–1385, 2011.
[23]
J. J. Roberts and J. M. Pascoe, “Cross-linking of complementary strands of DNA in mammalian cells by antitumour platinum compounds,” Nature, vol. 235, no. 5336, pp. 282–284, 1972.
[24]
S. E. Sherman and S. J. Lippard, “Structural aspects of platinum anticancer drug interactions with DNA,” Chemical Reviews, vol. 87, no. 5, pp. 1153–1181, 1987.
[25]
R. Barbieri, G. Alonzo, and R. H. Herber, “The configuration and lattice dynamics of complexes of dialkyltin(IV) with adenosine -monophosphate and phenyl phosphates,” Journal of the Chemical Society, Dalton Transactions, no. 4, pp. 789–794, 1987.
[26]
Q. Li, P. Yang, H. Wang, and G. Maolin, “Diorganotin(IV) antitumor agent. (C2H5)2SnCl2 (phen)/nucleotides aqueous and solid-state coordination chemistry and its DNA binding studies,” Journal of Inorganic Biochemistry, vol. 64, no. 3, pp. 181–195, 1996.
[27]
Q. Li, P. Yang, E. Hua, and C. Tian, “Diorganotin(IV) antitumour agents. Aqueous and solid-state coordination chemistry of nucleotides with R2SnCl2,” Journal of Coordination Chemistry, vol. 40, no. 3, pp. 227–236, 1996.
[28]
Z. Yang, T. Bakas, A. Sanchez-Diaz, C. Charalampopoulos, J. Tsangaris, and N. Hadjiliadis, “Interaction of Et2SnCl2 with -IMP and -GMP,” Journal of Inorganic Biochemistry, vol. 72, no. 3-4, pp. 133–140, 1998.
[29]
A. Atkinson, M. D. Rodriguez, T. E. Shewmaker T., and J. A. Walmsley, “Synthesis and characterization of compounds of di- and tributyltin chloride with adenine and guanine mononucleotides,” Inorganica Chimica Acta, vol. 285, no. 1, pp. 60–69, 1999.
[30]
H. Jankovics, L. Nagy, N. Buzás, L. Pellerito, and R. Barbieri, “Coordination properties of adenosine- -monophosphate and related ligands towards Me2Sn(IV)2+ in aqueous solution,” Journal of Inorganic Biochemistry, vol. 92, no. 1, pp. 55–64, 2002.
[31]
M. Sekine, T. Kamimura, and T. Hata, “A convenient method for the synthesis of P1-(7-methylguanosine- ) P2-(ribonucleoside- ) diphosphates,” Journal of the Chemical Society, Perkin Transactions 1, pp. 997–1000, 1985.
[32]
M. Nath, S. Pokharia, X. Song et al., “New organotin(IV) derivatives of dipeptides as models for metal-protein interactions: in vitro anti-tumour activity,” Applied Organometallic Chemistry, vol. 17, no. 5, pp. 305–314, 2003.
[33]
M. Nath, R. Yadav, G. Eng, T. T. Nguyen, and A. Kumar, “Characteristic spectral studies, and antimicrobial and anti-inflammatory activities of diorganotin(IV) derivatives of dipeptides,” Journal of Organometallic Chemistry, vol. 577, no. 1, pp. 1–8, 1999.
[34]
M. Math, R. Yadav, G. Eng, and P. Musingarimi, “Synthesis, spectral studies, in vitro antimicrobial and in vivo multi-infection antifungal activities in mice of new organotin(IV) derivatives of amino acids,” Journal of Chemical Research—Part S, no. 8, article 409, 1998.
