Recent development in synthesis and biological application of organotin complexes
Nitesh Jaiswal, Raj Kuamr Dubey*
Department of Chemistry, University of Allahabad, Allahabad-211002, India.
*Corresponding Author E-mail: rajalkoxy@yahoo.com
ABSTRACT:
Biological activities of organotin(IV) complexes with Schiff bases and organic ligand have been well established. Organotin complexes are getting significant attention, despite of the toxic concern, due to its wide spectrum of applications. The core area of research interest in organotin arises from its use as anticancer, antimicrobial, anti-inflammatory and other important biological activities. The present review provides a comprehensive idea to the people working in field of inorganic or organometallic synthesis with tin metal and covers recent development happened in last five year (>1000 research papers have been published in last five year) to get future perspective for fruitful result.
KEYWORDS:Organotin complexes, Schiff base, anticancer, antimicrobial and anti-inflammatory.
Pharmaceuticals needs are the core driver for unprecedented growth in metal based drug development research. During the last few years it is noticeable that organotin compounds occupy an important place in cancer chemotherapy reports. Optimistic result shown by tin complexes as metallotherapeutics inspired research to explore this field more precisely. Now, It has been well established that organotin(IV) compounds are very important in cancer chemotherapy because of their cytotoxic effect[1-5], ability to bind with DNA[6-9], antiprolifarting nature[10-13] and apoptotic inducing character[14-16]. Besides being a chemotherapic agent in cancer, organotin complexes with organic ligand or Schiff base screened for their role in antimicrobial[17-22] antibacterial[23-27] and anti-inflammatory activities[28-32].
Furthermore, Organotin complexes show the most diverse segment of applications ranging from material science[33-36] to catalysis activities[37-38] to therapeutic agent[39-40] for various diseases due to its wide variety of interesting structural possibilities.
Organometallic complexes pursue special advantage at structural and synthesis level and application of complex can be modified accordingly by considering metal and organic moiety. Flexibility of one or more Sn-C bond as mono-, di- and tri-alkyl/phenyl tin provide structural diversity to tin complexes for different applications. This makes organometallic complexes and specifically tin and organotin complexes more significant for application point of view. A limitation which needs due concern during synthesis of tin complexes is its side effects and toxicity.
Bioactivities of organotin complexes:
Organotin complexes are well known for its cellular activities which makes its role significant in antitumor, antimicrobial, antibacterial, anti-insecticidal, anti-inflammatory activities as well as in metallodrugs for treatment of various diseases. Out of these applications, their anti-cancer abilities have been studied most extensively.
Antitumor/Anticancer activities:
The use of organometallic compounds as a medicine is very common now a days because it offers potential advantages over the more common organic-based drugs. Several organotin complexes present lower IC50 values than those of cisplatin, which indicates their high activity against the cancer cell lines. The literature data reveal that every year new organotin(IV) complexes are synthesized with the aim of new anticancer agent with much better results than the corresponding activity of cisplatin or other clinically approved drugs.
The discovery of new non-covalent interactions with the classical target, DNA, was the first developing step in the treatment of cancer. Different route of mechanism at cellular level has been reported for action of organotin compounds toward cancerous cell. Organotin compound inhibits ATP synthase which cause death to cell. Apoptosis by tin complexes increase intracellular Ca2+ concentration, followed by reactive oxygen species formation and cytochrome c release from mitochondria, caspase activation, and finally DNA fragmentation. Organotins can also damage or cleave DNA by reacting with the phosphate group of DNA and intercalating into DNA.
Salicyaldehyde and thiosemicarbazone derivative organotin complexes[1,2] exhibits good amount of cytotoxicity against cancerous cells. Salicyaldehyde with other carbazones also screened positive in vitro cytotoxicities and DNA/BSA interactions[3, 6, 11]. Hong et. al [3] reported n-butyltin(IV) complex as better antitumor agent on three cancer cell lines, namely HCT-8, HL-60 and A549, than the methyl-, phenyl- or benzyltin(IV) derivatives. Salicyaldehyde with aniline and its derivative Schiff base organotin complexes (prove their credential in DNA interaction and cleavage[7,8] (Scheme 1a-c, g-j).
Di- and triorganotin complexes of ortic acid have been synthesized characterize and tested positive in vitro anti-cancer and DNA fragmentation [9]. Organotin complexes based on 2,6-di-tert-butyl-4- mercaptophenol exhibit significantly lower cytotoxic activity against normal MRC-5 cell line compared to the tumor cell lines MCF-7 and HeLa used. The IC50 against normal cell line MRC-5 is two-fold higher than that toward tumor cell lines. This result opens up the possibility of designing novel anticancer drugs that might possess lower undesirable toxicity against normal cells [10].
Antimicrobial activities:
Recently Roy and co-workers reported the synthesis of diorganotin(IV) complexes with an azo-imino carboxylic acid ligand (Scheme 1d) and also screened for their antimicrobial activities[20]. Some new diorganotin(IV) derivatives of N’-(2-hydroxybenzylidene)formohydrazid has been synthesized and produce good result as antibacterial, antifungal and leishmanicidal agents[21]. Tetradentate ligands bearing hydrazone and/or thiosemicarbazone motifs and their diorganotin (IV) complexes (Scheme 1e) has been synthesized and characterized by spectroscopic technique[22]. The antimicrobial activity of the ligands and these diorganotin(IV) complexes was investigated in vitro against seven species of microorganisms and minimum inhibitory concentrations (MICs) were determined. The results showed that the ligand and several of its derivatives, together with methyl and phenyl complexes, have the ability of inhibiting the growth of tested bacteria and fungi to different extents. Bacillus subtilis and Staphylococcus aureus Gram positive strains were the most sensitive microorganisms. Noureen and co-workers[23] synthesized a series of fluorine substituted organotin(IV) dithiocarbamate (Scheme 1f) and incorporate efficient strategy to identify pharmacophores and anti-pharmacophores sites in dithiocarbamates derivatives for antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out. The synthesized complexes have negative values of miLogP which indicate their ability to penetrate through bio-membranes, indicate their ability to penetrate through bio-membranes.
a b
C
d
F
g
i
j
Scheme1. A representative structure of some organotin(IV) complexes which have shown significant biological activities
Rehman et al [24] synthesized a novel series of diorganotin (IV) complexes of the Schiff base ligand derived from 7-methoxy-2-hydroxy-1-naphthaldehyde, 1,2- phenylenediamine, Salicylaldehyde and this newly synthesized tin (IV) complexes exhibit within a reasonable limit to excellent antibacterial activity.
Anti-inflammatory activities:
Inflammation or swelling is caused by release of chemicals from tissues and migrating cells. Tin complexes have shown positive result as anti-inflammatory agents. Di- and triorganotin derivative of fatty acid like lauric, stearic and myristic acid has shown anti-inflammatory activities[13]. Mala Nath and collaborator synthesized dimethyltin(IV)/diphenyltin(IV) and tri-i-propyltin(IV) derivatives of guanosine which were screened for their anti-inflammatory activities [26]. Some new tri- and diorganotin(IV) complexes of Schiff base [derived from condensation of tris(2-aminoethyl)amine and 4-methyl-5-imidazolecarboxaldehyde] have been synthesized and tested for their anti-inflammatory activity and toxicity[28].
CONCLUSION:
A holistic survey of last five-year research in area of organotin is very promising and will see new dimension in upcoming year. Researcher thrust to design and architect tin complexes at molecular level will further reduce its side effect and increase its effectiveness at targeted cellular cites. New techniques need to be incorporated for further investigation of action mechanisms of the organotin-Schiff base complexes at cellular level. The potential applications of organotin-Schiff base complexes rationalize an uninterrupted development of new molecules to eliminate the misconception that all organotin-compounds should be banned due to their toxicity concern. To achieve biological activities at ultra-trace levels, moving from the selectivity to the specificity level, with minimum undesirable side effects and low toxicity, more attention should be needed to perform molecular design-based research of organotin compounds.
ACKNOWLEDGEMENT:
One of the author (Nitesh Jaiswal)is thankful to University Grant Commission (UGC), New Delhi for providing doctoral fellowship.
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Received on 30.04.2017 Modified on 25.05.2017
Accepted on 03.07.2017 © AJRC All right reserved
Asian J. Research Chem. 2017; 10(4):436-440.
DOI:10.5958/0974-4150.2017.00072.4