Abstract
Considering the well-established antifungal activity of azole compounds, a new series of thiazolyl-methylen-1,3,4-oxadiazolines derivatives were designed and synthesized as lanosterol-demethylase inhibitors. The final compounds were screened for antifungal activity against the Candida albicans ATCC 90028 strain. Molecular docking studies were performed to investigate the interaction modes between the compounds and the active site of lanosterol 14a-demethylase, which is a target enzyme for anticandidal azoles. Theoretical ADME predictions were also calculated for the final compounds 5a-h.
Highlights
Experimental part ChemistryMelting points were determined using open capillary tube method and are uncorrected. The purity of the synthesized compounds was verified by thin layer chromatography (TLC) and was carried out on pre-coated Silica Gel 60F254 sheets using heptan–ethyl-acetate 7:3 as developpant and UV absorption for visualization
Considering the well-established antifungal activity of azole compounds, a new series of thiazolyl-methylen1,3,4-oxadiazolines derivatives were designed and synthesized as lanosterol-demethylase inhibitors
Following our research of novel azole based antimicrobial agents [15-17], we propose here the synthesis of some novel thiazolyl-methylen-1,3,4oxadiazolines derivatives as possible antifungal agents
Summary
Melting points were determined using open capillary tube method and are uncorrected. The purity of the synthesized compounds was verified by thin layer chromatography (TLC) and was carried out on pre-coated Silica Gel 60F254 sheets using heptan–ethyl-acetate 7:3 as developpant and UV absorption for visualization. Compounds 2a-b were synthesized by refluxing a mixture of benzothioamide or 4-methyl-benzothioamide (30 mmol) with ethyl 4-bromo-3-oxobutanoate (30 mmol) in absolute ethanol (30 mL) for 1 h. The reaction mixture was cooled yl)methyl)-1,3,4-oxadiazol-3(2H)-yl)ethanones 5a-h–. NMR m.p. 142(DMSO-d6, 97CH.O056C(c5H(H:s31)p1.-(hH2e, -nt(hy4li,a-4nzHoitlepro--5Bp)r,h-p4eh.0ne4ynly()sl)-,,527-H.(3(,72C(-Hsp12h)H,e,2no.y2xl6atdh(isiaa,zz3oHol l,C-N24)--, yl)methyl)-1,3,4-oxadiazol-3(2H)-yl)ethanone δ, ppm) δ: 11.49 (s 1H, NH), 8.51 (s 1H, -N=CH-Ph), 7.497.94, 9H (5H phenyl, 4H p-Cl-phenyl), 7.0 D6, δ, ppm) δ: 11.58 (s 1H, NH), 8.65 (s 1H, -N=CH-Ph), Cm2/1zH4181C3lN(3MO+2S2;)Y, i1eHldN7M0R%.(DmM.pS.O1-6d06-,1δ6,5p0Cp,mM)Sδ(:E7I.,2760-7e.V87):, 9t(hsH,ia53(zf4Ho:H,le1Nt--o5-(Cl)2y,Ol-,4(C44.0HH-6f3lo)u(.-sCo, lr2-opHph,ehCneHynl2,y)1,l )H2-.,53o-4(x(a(2sd-,i(a3pzH-ot,lotCol y2l)yl,)l-t7Ch.0Hi6a3)z(,os2l1.-2H43-, 7.47-8.03, 10H (2 phenyl), 7.24 (s 2H, 2 thiazole-5), 4.02 (s, y l ) methyl ) - 1 , 3 , 4 - oxadiazol - 3 ( 2 H ) - y l ) ethanone. Visualization and analysis of the docking results were performed using UCSF Chimera [22]
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