Dibutyltin(IV) complexes containing arylazobenzoate ligands: chemistry, in vitro cytotoxic effects on human tumor cell lines and mode of interaction with some enzymes

Abstract

Dibutyltin(IV) complexes of composition Bu₂Sn(LH)₂, where LH is a carboxylate residue derived from 2-[(E)-(5-tert-butyl-2-hydroxyphenyl)diazenyl]benzoate (L¹H) with water molecule (1), 4-[(E)-(5-tert-butyl-2-hydroxyphenyl)diazenyl]benzoate (L²H) (2) and 4-[(E)-(4-hydroxy-5-methylphenyl)diazenyl]benzoate (L³H) (3), were synthesized and characterized by spectroscopic (¹H, ¹³C and ¹¹⁹Sn NMR, IR, ¹¹⁹Sn Mössbauer) techniques. A full characterization was accomplished from the crystal structure of complex 1. The molecular structures and geometries of the complexes (1a i.e. 1 without water molecule and 3) were fully optimized using the quantum mechanical method (PM6). Complexes 1 and 3 were found to exhibit stronger cytotoxic activity in vitro across a panel of human tumor cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. Compound 3 is found to be four times superior for the A498, EVSA-T and MCF-7 cell lines than CCDP (cisplatin), and four, eight and sixteen times superior for the A498, H226 and MCF-7 cell lines, respectively, compared to ETO (etoposide). The mechanistic role of cytotoxic activity of test compounds is discussed in relation to the theoretical results of docking studies with some key enzymes such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II associated with the propagation of cancer.

Synthesis, characterization and crystal structures of 2-[(E)-2-(4-hydroxy-3,5-dimethylphenyl)-1-diazenyl]benzoic acid and its polymeric and monomeric triorganotin(IV) complexes

“…Further, these ligands and their analogues have been explored for their coordination behaviour towards organotin(IV) in order to find possible candidates in this class of organotin(IV) complexes which might act as anticancer drugs owing to their remarkable cytotoxic activity that has been exhibited in some cases across a panel of cell lines [3][4][5]. As a result of promising cytotoxic activity [6,7], the mechanistic role of these organotin(IV) compounds was investigated, to see influence of the azo group nitrogen atoms, by docking studies with some of the key enzymes such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II that take part in the synthesis of raw materials for DNA and its replication [3][4][5]. The docking studies indicated that the azo group nitrogen atoms and formyl, carbonyl and ester oxygen atoms in the ligand moiety play an important role.…”

Molecular basis of the interaction of novel tributyltin(IV) 2/4-[(E)-2-(aryl)-1-diazenyl]benzoates endowed with an improved cytotoxic profile: Synthesis, structure, biological efficacy and QSAR studies

“…We recently investigated the cytotoxic potential of triphenyltin (IV) 2-[(E)-2-(aryl)-1-diazenyl]benzoates and dibutylbis{2-[(E)-2-(aryl)-1-diazenyl]benzoato}tin(IV) and found to exhibit high activity when tested in vitro against human tumor cell lines [17,18]. Among these, the triphenyltin(IV) compounds were found to be better performers than dibutyltin(IV) compounds.…”

“…Among these, the triphenyltin(IV) compounds were found to be better performers than dibutyltin(IV) compounds. Further, the molecular docking studies of these compounds indicated that the azo group nitrogen atoms and formyl, carbonyl, ester and hydroxyl oxygen atoms in the ligand moiety exhibit hydrogen bonding interactions with the active site of the amino acids of various enzymes, such as ribonucleotide reductase, thymidylate synthase and thymidylate phosphorylase [17,18]. The high activity was attributed to the presence of an azo group in the organotin(IV) complexes molecules [17,18].…”

“…Further, the molecular docking studies of these compounds indicated that the azo group nitrogen atoms and formyl, carbonyl, ester and hydroxyl oxygen atoms in the ligand moiety exhibit hydrogen bonding interactions with the active site of the amino acids of various enzymes, such as ribonucleotide reductase, thymidylate synthase and thymidylate phosphorylase [17,18]. The high activity was attributed to the presence of an azo group in the organotin(IV) complexes molecules [17,18]. In this paper, we present the synthesis of a new series of complexes where the 2/4-[(E)-2-(aryl)-1-diazenyl]benzoate ligands are substituted with tributyltin(IV) (Scheme 1) in the expectation that they will improve dissolution properties and thereby influence cytotoxicity.…”

Synthesis, spectral, 3D molecular modeling and antibacterial studies of dibutyltin (IV) Schiff base complexes derived from substituted isatin and amino acids

“…The interest in organotin compounds in general and organotin carboxylates in particular continues to grow because of their biological activity and potential antineoplastic, antituberculosis agents [21,22]. Among those compounds dibutyltin derivatives have displayed both higher activity and lower toxicity [23]. Organotin complexes derived from carboxylic acids are among the most extensively studied class of compounds owing to their rich structural chemistry.…”