Browsing by Subject "THIAZOLE"

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  • Aly, Ashraf A.; Bräse, Stefan; Hassan, Alaa A.; Mohamed, Nasr K.; Abd El-Haleem, Lamiaa E.; Nieger, Martin; Morsy, Nesrin M.; Abdelhafez, Elshimaa M. N. (2020)
    A new series of methyl 2-(2-(4 '-[2.2]paracyclophanyl)-hydrazinylidene)-3-substituted-4-oxothiazolidin-5-ylidene)acetates3a-fwere synthesized from the reaction of paracyclophanyl-acylthiosemicarbazides2a-fwith dimethyl acetylenedicarboxylate. Based upon nuclear magnetic resonance (NMR), infrared (IR), and mass spectra (HRMS), the structure of the obtained products was elucidated. X-ray structure analysis was also used as unambiguous tool to elucidate the structure of the products. The target compounds3a-fwere screened against 60 cancer cell lines. They displayed anticancer activity against a leukemia subpanel, namely, RPMI-8226 and SR cell lines. The activity of compound3awas found as the most cytotoxic potency against 60 cancer cell lines. Consequently, it was selected for further five doses analysis according to National Cancer Institute (NCI) protocol. The cytotoxic effect showed selectivity ratios ranging between 0.63 and 1.28 and between 0.58 and 5.89 at the GI(50)and total growth inhibition (TGI) levels, respectively. Accordingly, compound3aunderwent further mechanistic study against the most sensitive leukemia RPMI-8226 and SR cell lines. It showed antiproliferation with IC50 = 1.61 +/- 0.04 and 1.11 +/- 0.03 mu M against RPMI-8226 and SR cell lines, respectively. It also revealed a remarkable tubulin inhibitory activity, compared to colchicine with IC50 = 4.97 mu M/mL. Caspase-3, BAX, and Bcl-2 assays for3ausing annexin V-FITC staining revealed significant pro-apoptotic activity. Furthermore, multidrug-resistant leukemia SR cells were used to show better resistance indices (1.285 ng/mL, 1.15-fold) than the reference. Docking studies with beta-tubulin indicate that most of the tested compounds illustrated good binding at the colchicine binding site of the enzyme, especially for compound3a, which made several interactions better than that of the reference colchicine.
  • Hassan, Alaa A.; Mohamed, Nasr K.; El-Shaieb, Kamal M. A.; Tawfeek, Hendawy N.; Bräse, Stefan; Nieger, Martin (2016)
    2-{Amino-[5-amino-2-(substituted diazenyl) thiazol-4-yl] methylene} malononitriles were synthesized from the reaction of 2-substituted hydrazinecarbothioamides with tetracyanoethylene (TCNE) to give tetracyanoethane adduct, followed by heterocyclization afforded the target compounds. The structure of (E)-2-{amino-[5-amino-2-(phenyldiazenyl) thiazol-4-yl] methylene} malononitrile was supported by single crystal X-ray crystallography.
  • Hassan, Alaa A.; Aly, Ashraf A.; Mohamed, Nasr K.; El-Shaieb, Kamal M.; Makhlouf, Maysa M.; Bräse, Stefan; Nieger, Martin; Brown, Alan B. (2020)
    The reaction between N-substituted alkenylidene hydrazinecarbothioamides and two molar amounts of tetracyanoethylene (TCNE) in anhydrous THF at room temperature without using any catalyst affords (Z)-4-amino-3-((Z)substituted amino)-2-(substituted imino)-2,3-dihydrothiazole-5-carbonitriles and (Z)-(4-amino-5-cyano-thiazol-2(3H)-ylidene)carbonhydrazonoyl dicyanides. Rationales for these transformations are presented. The structures of the obtained products were confirmed via single-crystal X-ray analyses. Graphic Here, we synthesize (Z)-4-amino-3-amino-2-imino-2,3-dihydrothiazole-5-carbonitriles and (Z)-(4-amino-5-cyano-thiazol-2(3H)-ylidene)carbonhydrazonoyl dicyanides from the reaction of N-substituted alkenylidene hydrazinecarbothioamides with (TCNE) in anhydrous THF at room temperature without using any catalyst. [GRAPHICS] .