Triorgano- Metal Derivatives of Some Carboxylic Acid Containing Drugs: Synthesis, Characterization & Biological Activities

Abstract

In this study, ten new series of triorganotin(IV) derivatives of carboxylates have been synthesized in a result of reaction between tri-organotin(IV) chlorides or tri-organotin(IV) hydroxides with carboxylate ligands of highly active and renound medicines of famous family of quinolones, flouro quinolones and few other such drugs in dry toluene. The ligands (HL1-HL10) used themselves very famous for their activities against most of the bacterial and fungal strains. The mode of coordination of these ligands, structural confirmation and geometric assignments of all the synthesized complexes (1-60) both in solid and liquid states were checked, using various analytical techniques in combination such as FT-IR, multinuclear (1H, 13C and 119Sn) NMR, CHNS analysis, mass spectrometry, TGA-DSC and single crystal X-ray analysis. On the basis of these results, most of the ligands appeared to coordinate to Sn atom through carboxylate moiety except thiobenzoic acid due to the formation of dimer. The trimethyltin (IV) and tributyltin(IV) derivatives posses trigonal bipyramidal geometry both in solid and solution state while triphenyltin(IV) have shown tetrahedral geometry specially due to bulky nature of phenyl groups. The binding/interaction of newly synthesized compounds with SS-DNA was checked by UV-visible Spectroscopic technique and on the basis of viscosity measurement method in the presence and absence of complexes. A hypochromic effect along with obvious bathochromic shift (red shift) was seen in UV studies. These are the clear indications of intercalation mode of interaction. The complex-DNA adduct was formed with great spontaneity as does indicated by the negative values of ∆G for all the evaluated complexes. These results were also well supported by complex-DNA intercalation when checked by viscosity measurement method. All of the newly synthesized complexes were also checked in terms of their antibacterial and antifungal behaviour against several different medically important bacterial and fungal strains whose culture were already prepared and was taken from market. All of the new triorganotin (IV) derivatives have shown significant antibacterial and antifungal activities, more than their respective ligands. Furthermore, most of the newly synthesized compounds were found to have fair antimicrobial activities comparable to the reference drugs. These observations gave the idea that most of these compounds may potentially be used as effective antibacterial and antifungal agents in the coming future. The antitumor and anticancer behaviour of the representative complexes were very positive especially when antitumor agent not only could serve for the treatment of tumors but also can act as a potential source of chemo protective agent which was the worst challenge for all the chemists who are presently working in the field of medicinal synthesis. The leishmaniocidal activities of few of the synthesized compounds were also evaluated and it was found that some of the compounds have shown strong antileishmanial activities. Therefore, the results demonstrated that these synthesized complexes can potentially be used as a new source of novel agents for the effective treatment of leishmaniasis.