Alikhani, Nikisadat

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,,, ;r', : _,-";,i-,iu.F u+b.)'r .i*ilq-r crLo'rs J 'rsJ'ii fJls ot(fiIlr' ,r"/':'';** rsf3;l.r fJJs g cfjt* ,S3l,r o.rS.liil,l#-g**B;ggjL*r33l,r s'lg s gfJiS, +.LiU!h(,s.r,6JiiJJiI )-Y)-t-e;tf-0-&tu-Y crt5:*i,"0 CSstS" S,j.f, J }i.*rCO.rsl",r.; Jt*6 ogsJt,, &f g. 0 l3js *.r Jgj l.ru.rl-ru- (i.J.r:l:Ja*-r3n.'il i..r la gl.rL*, ."+:La.ial; +L-,f.,JljJ*" tSu Ot*,-f jsuo.rl1 g*Lrs ct,{i }S.lq AY :+cliuLr! o;t-o.i \ f 12 ot-o ,i-t+Jan 2018Kerman Univercity of Medical SciencesFaculty of PharmacyFor the Certificate of Pharm.D. DegreeSynthesis and Molecular Docking of 2-Methyl-5-nitro -l-(2-(nitrophenoxy)ethyl)-1tl-imidazole Derivatives as PotentialAnti-microbial AgentsBy:Niki sadat AlikhaniSupervisors:Dr. E. FaghihmirzaeiDr. M. AbbaszadehThesis No: 2534.2Lt v)*'rsb *t;"f-j, t G-J)l).--3lL ) -y- S.- -,1 ,l-i-t-,i:t J ,5|2G,.,1L-rS! 5Lo c;rlr -;;:+o-iLJt* o-.,+.:[5r ciL: ;LL*l q jt! ,-K-, tSs* -:t i-SE-S gG3;ir JL ."-r-r .-era.i:-t) jj;* dJL,-i #, ;"^" a, .c.*1 o:r5 rt--l l-' ,u,.! ts" isb g;Lr a-1_* J 6 ;*..)Lal;j-ryX -r t*:-U1." g-r-,.1! 6.1--te OWi *- 6:-: J..JL$- ,ul1- st 6;L3_;1.:,ri-J-rlr .,."-J F;^" J:+ t:s,.gtr;*J) jl "! Ji;4.1 ;r .C*1 *\;-3 ],e-t\ ls^L^JI}L- ;r--l jl .._&.-;!f ./^i ori a;;L; -,BL .i" .rLl , -u--t- gL^i-*(_r" ;-SJj;l-q! s Jtl4tf -uJL .ri;;l: o!5r :l u-t;: e5 u[.r" J;;l-t"--l ,F"-Y-:;,-0,5rl.r; arL- -r J:jl+--l p-Y-;;-0 Jf(y" ;:J* .,.*-r, ,))V -.-AJi ;,: .r;lr ry>-3"* ;:\f .:r!5r .rLl -t ,-,1:l ;r *--l a:sf :l; ,s-:-t );;'r n:-) ;-l ;1 r1.-i.7 .-rL,i:- ;l6.;i "- JLa:l .iul;r olr- ,-Ll -i Gji Jt"Fq ei ;t,d,q..Si ai.1 q,.; d-,[rL ! };&.5t. ers-: )l orLl-*l L .:;1: t^,SF! GV =f dt^+-l -*h;) .-r^4- _;J ,.5 FabH.;*\ ^*f :1; "r-:t. t-,s" J-#_r.r-u; j- ;t.r p--;i<" t .t<i{t"ji;r 5a-e -, 3 -f-Sj t-i:l :;t5 ei,r-)NO./-lN. l, 'Y''*onI 3NO.,.r",,*f I"*oS*-,9.'oQ* G,II sf)b v,'2d# .-\-i fL+jl 13CNMR , 1HNMR JR r5L-a-;-t L-; ,* jL" .i$i rU-L Ji.*iOpen ;lilgrr 1l ..rLi;l ! I g*-, ChemDraw ,l;clg-,, -rr dJ,.r -2t ,J;3* y -E >t-r .)$-i*l3--"1 q-Uq olie\AutoDock 4.2;l;\, .'' J.-,o)LL-"\,Slt,s.Lq{i1",,i,Jjr,lBabelj (^!U;r Protein Data Bank c--L ,1 51i J-i-(rJrSt !t-G r- ..1-r" J) .-Ll-ti .r"=! pdbo-L.; ulL,cLrJtKJ ll oll5-a 4i[<l]- ,J--,.:J\ <q\ J Ai\,<l-a;\ .o rlr;l il -l_tJvJJJ.-t.:uvrJJ.\Jo"t.,-\JUr. JrJ ; -,1 ; r) -# -y.,S-,L J-t" .:;;* AutoD ock 4.2 r\ y\ 1 y L* t.tK-:-U;i;r c*ji-i_9* L .:La:- ,_/L-i nt Jrlr gL:i '3CNMR j 'HNMR JR .5t-"-,q-t :e-'itJ.-Li>l.: eL-:.i )_i )\ l-t J* JU Jt '1 Sjtl J_fl_r UjLJ-t" "r_,-, ! y -tJl ou ;;:*Gf A,. or; _;:-- Jl;ii-^ ./L"J ,JF r^ S;Stt ji J.-f eUj t ^i;', q :6$^V"S J e-..t-r *rj-r-,r-o -t-iJi:- J.-=" ;r-l .JL^-+-t-r+I q J )-:1, 5f ,11FabH Cj-1 Jt"j .K-F ,,j o.C f c--*i AG U";^S ;;;1, q 5e .Jj oI; -F" -ruii- ;- ;i .I:t' itt .S-*ss*.-,t-,=:ll insilico J-t- ,r FabH ,',-;i or5;L6. -:5 i ,1.*,JlJ:, q ,aj-l-,{- S*l ;r..*.-LrJ-fl-* (5t, ,;;:* ,J;1[*.13i .--,Li; :d45 crLJsAbstractAbstractIntroduction: The development of bacterial, fungal and protozoal infections on the onehand and drug resistance due to the use of several drugs for many years on the otherhand, it has been required the identification and construction of new active bioactivecompounds that are effective on resistant strains. For this reason, the activities ofpharmaceutical researchers around the world have been expanding to synthesize newcompounds that are potentially effective on microbes and protozoa.ln the meantime,one of the accepted methods of medicinal researchers is development of new moleculesbased on a previously known structure. One of these structures is 5-nitro-2-methylimidazole, which is present in some already drugs, such as metronidazole andtinidazole. In the present study, a further development of 5-nitro-2-methylimidazoleskucture and the synthesis of a number of new derivatives from this category have beeninvestigated. Subsequently, on the basis of previously reported works. the antibacterialeffect of our new compounds was evaluated on the ability of binding to the FabHenzyme that plays an important role in the biosynthesis of vital fatty acids of bacteria,using a molecular docking method.Methodology: First, the compounds 3 and 5a-e were synthesized according to thefollowing procedure:mNO"l<Yo**1s*,,9+3='m">S;,,,9)^(*o'DMF :- f...rco,,rr;a- "Y**o*Q,4a-eA.$x5a-eThe strucfures of synthesized compounds were determined by IR, 1HNMR and l3CNMRspectra. Then, the components were drawn in ChemDraw software. The structures wereenergetically optimized by Open Babel software and they were saved in AutoDock 4.2software as ligand with pdb format. Then the 3D structure of the receptor (FabII) wasobtained from Protein Data Bank and following refening for docking simulation,fl* -t /f't-'loAbstract ryAutoDock 4.2 software was applied for molecular docking approach, for eachindividual designed ligand.Results: The IR, 1HNMR and l3ci.trlt4R spectra indicated that all the derivatives weresuccessfully synthesized in laboratory and they showed appropriate intermolecularbinding energy upon docking.Conclusion: According to the docking results, all the synthesized derivatives wereaccommodated properly in the active site of FabH enzyme and they made hydrogen andhydrophobic bindings with the appropriate amino acids. Amongst the synthesizedcompounds, compound 5e showed the best insilico inhibitory activity against enzpeFabH due to its lowest AG and highest lipophilicity.Keywords : Nitroimidazole Derivatives, S ynthesis, Molecular Do ckingF-/ik-"i{ffittE-,+IehJt sihJ.) ,""et,t+ *k*i I u#:lp$ atitrifoG1U91tc e*$ifot&H o;t*i a{ t. 1S$S;S 151{*3;!+'rgpd,ifo dfu**[6 *ls[*Jl *Sg Fr{S e*[} ClQt:gfr*e ;*j,s t',,J t ) t4r ;N, - t { r W{,fi ;> - t- i.- * -,[ r,* f, 4 {, J{r,,r'',t,{*Corisa;'s:k*f;,ryLal;t""-'l 5: -lrq* i5, -Y;L"dl*igp Y*,* g irj, -sV; rs urig 5: -YU , lJ.! , / - /v) J -)\'\/KN.t*, t =p, ffr*"7: $rg,..(4 r,jJr)JsW- {A3s6i:l.1> Lb

Synthesis & molecular docking of 2- methyl-5-nitro-1( 2-( nitrophenoxy) ethyl) - 1H- imidazole derivatives as potential anti- microbial agents

http://eprints.kmu.ac.ir/27063/1/6471_20180408_0001.pdf

Synthesis & molecular docking of 2- methyl-5-nitro-1( 2-( nitrophenoxy) ethyl) - 1H- imidazole derivatives as potential anti- microbial agents

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