Docking of Cisplatin on Fullerene Derivatives and Some Cube Rhombellane Functionalized Homeomorphs

Beata Szefler,Przemysław Czeleń

doi:10.3390/sym11070874

Abstract

Cisplatin (cisPt) is one of the strongest anticancer agents with proven clinical activity against a wide range of solid tumors. Its mode of action has been linked to its ability to crosslink with the canonical purine bases, primarily with guanine. Theoretical studies performed at the molecular level suggest that such nonspecific interactions can also take place with many competitive compounds, such as vitamins of the B group, containing aromatic rings with lone-pair orbitals. This might be an indicator of reduction of the anticancer therapeutic effects of the Cisplatin drug in the presence of vitamins of the B group inside the cell nucleus. That is why it seems to be important to connect CisPt with nanostructures and in this way prevent the drug from combining with the B vitamins. As a proposal for a new nanodrug, an attempt was made to implement Cispaltin (CisPt) ligand on functionalized C60 fullerenes and on a cube rhombellane homeomorphic surface. The symmetry of the analyzed nanostructures is an important factor determining the mutual affinity of the tested ligand and nanocarriers. The behavior of Cisplatin with respect to rhombellane homeomorphs and functionalized fullerenes C60, in terms of their (interacting) energy, geometry and topology was studied and a detailed analysis of structural properties after docking showed many interesting features.

Highlights

Cisplatinum (Figure 1) is one of the strongest anticancer agents with proven clinical activity against a wi1d
The symmetry of the analyzed nanostructures is an important factor determining the mutual affinity of the tested ligand and nanocarriers
Theoretical studies suggest that nonspecific interactions of Cisplatin can take place with many competitive

Summary

Introduction

Cisplatinum (cisPt) (Figure 1) is one of the strongest anticancer agents with proven clinical activity against a wi1d. Ientrraondgucetioofn solid tumors [1,2,3,4,5]. As a chemotherapeutic drug it has been used for treatment of numerous huCmispalnatcinaunmce(rcsisPint)c(lFuigduinreg1l)uisngon, ebloafdthdeers,trtoensgteicstualanrti,chanecaedr ,aagenndtsnweicthk pcaronvceenrscli[n1i]caalnd ovarian carcinomasa[c4t]iv. ItIyt iasgaeiffnsetcatiwviedeargaanignesotfvsoalridiotuums toyrsp[e1s–5o].fAcsaanccheerms,oitnhecrlaupdeuintigc dcraurgciitnhoams baese,nluysmedpfhoromas, germ cell tumorst[r1ae]naatdnmdesnoavtraocrfoianmnucmaasercr[ion2uo]sm. Ioctadisneceefofresfcitanivcceltuiadoginanignhslatuvnsagbr,ieobuelasndtdyleipnre,skteoesfdticcatunolcaerir,tssh, eianabdcli,uladintiyndgntcoeacrckcricnoaosnmscelairsns, k with the canonical pluymripnheombaass,egse,rmprciemll taurmiloyrswanitdhsagrcuoamnaisn[e2],. AItns dmotdoeaofleacstsioenr heaxstbeenetn wlinikthedatodeitns ainbieli,tyfotound within double heliccraoslsDlinNk Aw.ithThthise icnantounricnalspeurriionue sblayseisn, tperrimfearreilsy wwiitthh gDuaNniAne,reapndaitroma elecshsearneixstmenst ,wciathusing DNA damage andamdesecunhibannsei,esqmfousu,encndautlwsyiintighniDndNudAocuidnbalgme aahgpeeloicapanltdoDssuNibsAs[e.6qT]uheiinnstlciynainntudcruencrinscegerliaolpsuo.splytosiniste[6rf]eirnescawncitehr. IAsPfttewripthasnsainnogsttrhurcotuurgehs athned cienlltuhlisarwbaayrrier, a rupmtbmuaarakrekreTioeehifrtia,ttpthaprieersrevucvweopenmhtntuytprthetilhteeoexsdfedwreturhmuogeugscflrtofdoormomobmpcelccecouixmomrmwpbabonionirudntilnaidtnghgtoewctwofcirtuihetcrheotanhtcnhneisdePBcBttthvcCveiotiatsfuarmPlemtdeiniwnicsni.sistt.AhPeArtfnatfcetacoerntrupowlpsadtiasrtssihunisncitbnteguagrartshetcehstrsorwaoiunnuigtdgthhhitebnhtahietsnehectisceeselrillwniuloulartalhyaroerf the cell (Fbiiangrtureirreiero,2ra)o.rfuthpetucreello(fFitghuereco2m). Plex would occur and the free cisPt could interact with bases in the interior of the cell (Figure 2). Only those have been used which have functional groups that allow attachment of CisPt (Figure 3) RonheoKmR2b.3hecoollmmanbpeelelsltamenbeaisypabmretaitsyeysnbutebhgesrsyainpztehhdoesraistzheredesamlamsalloreelseatclruhmloemos,lbewceulhllaiencshe, rrwbelph.5irc.ehsenretparenseewnt calasnseowf hcylapsosthoeftical structuhyrepsRo.thhoQemtiucbaelnlltsautnrmeusctcumarleacsyu. lQabuetiaonsnytsunmt(haetcsaitzlhceuedlaBta3iosLnYrseP(a/al6t-mt3h1oeGleBc(3udLl,eYspP, /)6w-l3eh1viGcehl (odrf,eppthr)eelseoevnreytl) oa[f1n4the,1ew5o]rycs)lua[sp1s4p,o1o5fr]t the hypohthsyueppsoiptshoterht iactthaltehsehtrsyuepcostuthrbessti.rsuQtcuhtauntrtetuhsme(saect aeslvucueblrsayttriuloecnvtsuerl(eaostft(chaotemeBvp3eLlreYyxPilt/ey6v-)3eal1rGoefe(dcno,emrpg)pelteixvcieatlyll)oyfafrteheaeseoinbryeler)gi[en1t4itc,h1a5ell]yhope of a rseufaeplapsiyobrnltethtihneestihshey[h1po6op–the2e0os]fi.sa trhealt styhnetsheesiusb[s1t6r–u2c0tu].res (at every level of complexity) are energetically TfehaesirbeTleahireneretmhaearehnomypateynopyfetaysrpoeefasltohsfyentshtehesseetsrisut[rc1ut6uc–tru2e0rse],.sa, mamoonnggwwhhiicchh oonnllyyththoosesehahvaevbeebeneeunseudsewdhiwchhhicahvehave functiofunnacTltihgoernroaeulapgrrseotmuhpaasnt ytahltalyotpwaellsoaowtftatahcthteasmcehesmtnretunoctfuoCrfeiCss,iPsatPm(tFo(Fingigguuwrrehe3i3c))h.. only those have been used which have functional groups that allow attachment of CisPt (Figure 3)

Methods

Results

Conclusion