Amino acetate functionalized Schiff base organotin(IV) complexes as anticancer drugs: synthesis, structural characterization, and in vitro cytotoxicity studies

Abstract

Potassium 2-{[(2Z)-(3-hydroxy-1-methyl 2-butenylidene)]amino}-4-methyl-pentanoate (L1HK) and potassium 2-{[(E)-1-(2-hydroxyphenyl)alkylidene]amino}-4-methyl-pentanoates (L2HK-L3HK) underwent reactions with PhnSnCl4-n (n = 2 and 3) to give the amino acetate functionalized Schiff base organotin(IV) complexes [Ph3SnLH]n (1-3) and [Ph2SnL] (4), respectively. These complexes have been characterized by 1H, 13C, 119Sn NMR, IR spectroscopic techniques in combination with elemental analyses. The crystal structures of 1 and 3 were determined. The crystal structures reveal that the complexes exist as polymeric chains in which the L-bridged Sn-atoms adopt a trans-R3SnO2 trigonal bipyramidal configuration with the Ph groups in the equatorial positions and the axial locations occupied by a carboxylate oxygen atom from one carboxylate ligand and the alcoholic or phenolic oxygen atom of the next carboxylate ligand in the chain. The carboxylate ligands coordinate in the zwitterionic form with the alcoholic/phenolic proton moved to the nearby nitrogen atom. The solution structures were predicted by 119Sn NMR spectroscopy. When these organotin(IV) complexes were tested against A498, EVSA-T, H226, IGROV, M19 MEL, MCF7 and WIDR human tumor cell lines, the average ID50 values obtained were 55, 80 and 35 ng/ml for triphenyltin(IV) compounds 1-3, respectively. The most cytotoxic triphenyltin(IV) compound in the present report (3) with an average ID50 value of around 35 ng/ml is found to be morer cytotoxic for all the cell lines studied than doxorubicin, cisplatin, 5-fluorouracil and etoposide. (3) with an average ID 50 value of around 35 ng/ml is found to be morer cytotoxic for all the cell lines studied than doxorubicin, cisplatin, 5-fluorouracil and etoposide.

Synthesis and Structures of Two Triorganotin(IV) Polymers R3Sn{O2CC6H4[N=C(H)}{C(CH3)CH(CH3)-3-OH]-p} n (R = Me and Ph) Containing a 4-[(2Z)-(3-Hydroxy-1-methyl-2-butenylidene)amino] benzoic Acid Framework

“…Similar additional weak Sn···O coordination was also observed in the structures of related polymeric [R 3 SnLH] n derivatives [12,17,27], in which the Sn···O distances are significantly longer than those observed in triphenyltin(IV) compounds 1 and 2. The formal hydroxy group has lost its H-atom, so it is negatively charged.…”

“…A strong sharp band due to the [ν asym (OCO)] stretching vibration of the free ligand (LHH') at 1699 cm -1 is shifted to ∼1636 cm -1 in 1 and 2 as a result of carboxylate coordination to the Sn atom [10,14,16,17,19]. [12,16,27,[31][32][33]. The δ values, shifted downfield with respect to the analogous triorganotin(O 2 -donor pyrazolonate) [33] complexes, testifies that the polymeric …”

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

“…The preference for the formation of the zwitterionic form of the ligand in complexes may be a result of the coordination of the phenoxide O-atom to the Sn-atom in 1 and 2 while a steric reason could be ascribed for 3 where such coordination is absent. However, quinoid or zwitterionic forms are quite commonly encountered in similar systems [25][26][27][28]. Table 2 Selected bond lengths (Å) and angles (º) for LHH' Primed atoms refer to the molecule in the symmetry related position: 1+x,-y,1/2+z Table 4 Selected bond lengths (Å) and angles (º) for 1-3 a 1 2 b Table 5 Hydrogen bonding geometry (Å, º) for 1-3 a a The H-bonding geometrical parameters for the four independent fragments of complex 2 are in square brackets while those of complex 3 are in parentheses.…”

Triphenyltin(IV) 2-[(E)-2-(aryl)-1-diazenyl]benzoates as anticancer drugs: synthesis, structural characterization, in vitro cytotoxicity and study of its influence towards the mechanistic role of some key enzymes

“…The promising development in the search for antitumour organotin(IV) compounds has been achieved with some triphenyltin(IV) carboxylates, such as 3,6-dioxaheptanoate and 3,6,9-trioxadecanoate [20], 4-carboxybenzo-15-crown-5 and 4-carboxybenzo-18-crown-6 [20,21], steroidcarboxylate [22] and terebate [17,19,23] when screened in vitro against human tumour cell lines, as per the NCI protocol. In view of the increasing interest in organotin(IV) carboxylates, a few organotin(IV) complexes of Schiff bases derived from amino acids have also been investigated extensively [24][25][26][27][28][29][30][31][32][33][34][35] and the in vitro cytotoxicity results demonstrated that triphenyltin(IV) compounds are generally more active than CDDP (cisplatin) [34,35]. On the other hand, examples of organotin(IV) carboxylate containing -N=N-skeleton are scanty except for the recent ones on the diorganotin(IV) compounds of the formulations n Bu 2 Sn(LH) 2 and {[ n Bu 2 Sn(LH) 2 ] 2 O} 2 (LH=5-[(E)-2-(aryl)-1-diazenyl]-2-hydroxybenzoate) and the in vitro cytotoxic results were quite promising at least with respect to the some of the standard drugs [36,37].…”