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Role of Bio-Metal Zn (II) in Anticancer Behaviour of Tamoxifen

2010; PANhealth Care Research Society; Volume: 3; Issue: 4 Linguagem: Inglês

0974-4169

Jyotsna Shukla, Brijesh Singh, K. S. Pitre,

Metal complexes synthesis and properties

Phys icochemical. mi crobial and pharmacological studies on Fe (III) - T amoxife n complex have been carri ed out in solid and aqueous phases. O n th e basis of ele ment al analys is, polarographi c studies, amperometri c titrati o ns and IR spectral ~tudies th e probable fo rm ula fo r the complex has been worked out to be I: I , Fe(II1 ) - T amoxife n. A tent ati ve structure has heen suggested to th e compl ex. The metal li gand inte rac ti o n has been studi ed usi ng polarographi c me thod at 27° ± 1°C and at io nic strength of 11 = 1.0 ( KCI). Microbial studies on the complex was carri ed o ut again st vari ous pathogeni c bacteria and rungi using Raper's meth od. Mo use sarcoma cell lin e 180 and Balb/C mi ce were used fo r the anti cancer screening of solid co mpex . ill \'ilm and ill vi vo, respecti vely. The results of mi crobi al and pharmacological studies with th e M:Drug complex revealed th at the complex is mo re pote nt as compared to th e pure drug .as regard s to it s anti cancer activit y. As such Fe (III ) Tamoxire n co mpl ex may be recommended to th e th erape utic expe rt s fo r it s possibl e use as mo re potent anti cancer drug. The biochemi cal, ph armacological and medi cin al import ance of metal-dru g complexes is very well establi shed :; . In continuati on to the work done in our laboratory on th e study of electrochemical, bi o­ in organi c, mi crobi al and pharmacological behavi our of some metal-dru g complexes 6 . 9 , the present paper deals with th e said studies on the Fe(lli)-Tamoxifen (2 -[p-( I ,2-diphenylbut-l-enly ) phenoxy] ethyl­ dimeth ylamine (anticancer drug) complex. Chemica l and reagents-All the chemicals used were of Ana lar/BDH grade . The drug Tamoxifen (C26 H29NO) was procured from Mis Lyka labs Ltd .. Bombay. Doubl e di still ed water and absolute me th ano l were used as solv ents. Po larographi c measurements were made on an Eli co (Hydrabad) pulse pol arograph model CL-90, coup1 ed with a X- Y polarocard model LR-IOS. A dropping mercury e lectrode (DME) as a working e lectrode, a coil ed pl atinum wire as an auxiliary e lectrode a nd saturated cal ome l electrode (SCE) as a reference e lectrode, were used . Ex periment al sets were prepared by keeping o ver a ll iron (metal ion) and potass ium chloride (supportin g e lectrolyte) concentration fixed at 1.0 mM and 1.0 M, respectively. The ligand concentrati o n was va ri ed from 0 .5 to 5 mM. The pH of th e test so luti on was adjusted to 7.0 ± 0 .2 using NaOH solution. The amperometric titrations were performed on a manu all y operated set-up, equipped with a polyflex galvanometer (sensiti vity S. I x I 09 ampJdiv.) and an AJCO vamier potentiometer. DME was used as an indicator el ectrode and a c al omal electrode served as reference electrode. The capillary characteristics of the DME had a m2IJ, t 6 values of 2. 13 mg2l3 Sec· t 12 at 50 cm effecti ve hight of mercury column. The pH of all the test solutions was measured on an Elico digital pH meter model LI-I OS . Experimetal sets, each having different but known amount of th e drug understudy were prepared in appropriate quantity of supporting electrol yte (potassium chloride) at pH 7 .0±0.2 were pre pared and titrated separate ly again st the standared soluti on of the titled Fe (ill) ions whose pH has been adjusted to that of the titrat e (7.0±0.2). Synthesis procedure of the solid complex-Ferri c chloride and T amoxifen (drug) solutions were separately pre pared in methyl alcohol (50:50 v/v) and were mixed in I: I molar ratio. The mixture was th en reflux ed in a round bottom flask for one-two hours. The res idue (complex) was filtered and washed th oroughly to remove any unreacted mate ri als. The complex was dri ed at low temprature (40°C) and stored over P40 JO . The elemental , C, H, Nand 0 analysis of th e complex was done on a coleman elemental anl yser model-29/33, at CDRL Lucknow, whereas gravimetric method was used for th e estimation of . . h I to Iron m t e comp ex .