in Wiley Online Library (wileyonlinelibrary.com).Synthesis of unreported hitherto N,N 0 -([1,1 0 -biphenyl]-4,4 0 -diyl)bis(2-cyanoacetamide) as a precursor to synthesize bis-chromenes, bis-thiazole derivatives, and bis-pyridizines. The structures of the newly synthesized compounds were established by their elemental analyses and spectral data. Some of the newly synthesized compounds were tested for in vitro activity against hepatocellular carcinoma, human breast cancer, and human cervical carcinoma cell lines compared with the employed standard antitumor drug (doxorubicin), and the results revealed that the starting N,N 0 -([1,1 0 -biphenyl]-4,4 0 -diyl)bis(2-cyanoacetamide) is more potent activity than doxorubicin against hepatocellular carcinoma and human cervical carcinoma.

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3‐(3,5‐Dimethyl‐1 H ‐pyrazol‐1‐yl)‐3‐oxopropanenitrile 1 was used as a cyanoacetylating agent for synthesis of the acetanilide derivative 3. Compound 3 was utilized as a key intermediate for the synthesis of some new mono‐chromene and di‐chromene derivatives 9 and 13, the dihydrazo derivatives 15, and the dithiazole derivatives 18 via the condensation with o‐hydroxybenzaldehyde derivatives, the coupling with aryl diazonium salts, or the reaction with phenyl isothiocyanate in presence of KOH followed by phenacyl bromide derivatives respectively.

Knӧvenagel condensation of the starting 2-cyano-N 0-(4-(2-oxo-2-phenylethoxy)benzylidene)acetohydrazide with different aromatic aldehydes produced the comparable arylidenes derivatives. Else way, 2-cyano-N 0-(4-(2-oxo-2-phenylethoxy)benzylidene)-acetohydrazide condensed with o-hydroxybenzaldehydes affording the respective chromenes which latter underwent acid hydrolysis giving the oxo-chromenes analogues. Moreover, the reaction of 2-cyano-N 0-(4-(2-oxo-2phenylethoxy)benzylidene)acetohydrazide with istain yielded the respective indeno [2,1-b]furan derivative that was converted to its oxo-analogue through acid hydrolysis. The treatment of 2-cyano-N 0-(4-(2-oxo-2-phenylethoxy)benzylidene) acetohydrazide with α-halocompounds produced the relevant thiazoles. The enamine 2-cyano-3-(dimethylamino)-N 0-(4-(2-oxo-2-phenylethoxy)benzylidene) acrylohydrazide underwent nucleophilic substitution reaction with guanidine hydrochloride followed by heterocyclization to get the relative aminopyrimidine. Contrarily, the reaction with various 4-arylazo-3,5-diaminopyrazoles provided the relative pyrazolo[1,5-a]pyrimidines. The antimicrobial investigation was carried out for some of the newly synthesized compounds using agar well diffusion method.

Arylmethylene derivatives, chromenes and aminothiophenes were synthesized from 2-cyano-N-(4-(3-(thiophen-2yl)acryloyl)phenyl)acetamide 2. The anticancer activity of most synthetic compounds was assessed in breast cancer (MCF-7), hepatocellular carcinoma (HepG-2) and cervical cancer (HeLa), with five of arylmethylene and chromene derivatives showing highest cytotoxic activity. Further, treatment of breast cancer (MCF-7) cell lines with 4 d and 6 b, the most cytotoxic compounds; revealed down regulation for ERK-2 protein with expression concentration; 527.7 � 6.61 and 427.7 � 8.39 pg/ml, respectively compared to staurosporine; 440.9 � 5.02 pg/ml. Moreover, cell death induction was assessed by Annexin V-FITC/PI assay and these compounds caused cell death by apoptosis, besides the DNA fragmentation was assessed by gel electrophoresis and ELISA and the data showed increase in the percentage of fragmentation in treated MCF-7 of values; 30.49 % and 28.19 % in 4 d and 6 b, respectively confirming the same effect as staurosporine. The DNA-flow cytometric cell cycle analysis showed that 4 d and 4 g arrested the cell cycle at S phase and 8 b arrested it at G1/S phase. Molecular docking was carried out together with physicochemical properties prediction using DruLiTo program.