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Curcumin, a widely utilized flavor and coloring agent in food, has been shown to demonstrate powerful antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. In the present work, synthesis of new heterocyclic derivatives based on Curcumin was studied. Compound 3 was synthesized via the reaction of furochromone carbaldehyde (1) with Curcumin (2) using pipredine as catalyst. Also, novel, 4,9-dimethoxy-5H-furo [3, 2-g] chromen-5-one derivatives 4a–d, 6a–d, 7, 8a–d, 9 and 10 were synthesized by the reactions of furochromone carbaldehyde (1) with different reagents (namely: appropriate amine 3a–d, appropriate hydrazine 5a–d, hydroxylamine hydrochloride, urea/thiourea, malononitrile, malononitrile with hydrazine hydrate). The structure of the synthesized products had been confirmed from their spectroscopic data (IR, 1H-NMR, 13C-NMR and mass spectra). In the present investigation, the newly synthesized products were screened using the MTT colorimetric assay for their in vitro inhibition capacity in two human cancer cell lines (hepatocellular carcinoma (HEPG2) and breast cancer (MCF-7) as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drugs: 5-flurouracil and doxorubicin. The anticancer activity results indicated that the synthesized products 4c and 8b showed growth inhibition activity against HEPG2 cell line and synthesized products 4b and 8a showed growth inhibition activity against MCF-7, but with varying intensities in comparison to the known anticancer drugs, 5-flurouracil and doxorubicin. Cyclin dependent kinase 2 (CDK2), a major cell cycle protein, was identified as a potential molecular target of Curcumin. Furthermore, Curcumin induced G1 cell cycle arrest, which is regulated by CDK2 in cancer cells. Therefore, we used molecular modelling to study in silico the possible inhibitory effect of CDK2 by Curcumin derivatives as a possible mechanism of these compounds as anticancer agents. The molecular docking study revealed that compounds 4b, 8a and 8b were the most effective compounds in inhibiting CDk2, and, this result was in agreement with cytotoxicity assay.

Microwave-assisted organic reactions have been applied as an effective technique in organic synthesis. Microwave irradiation often leads to shorter reaction times, increased yields, easier workup, matches with green chemistry protocols, and can enhance the region and stereo selectivity of reactions. In fact, the high usefulness of microwave-assisted synthesis encouraged us to increase the efficiency of several organic transformations and synthesis. High-speed microwave-assisted chemistry has attracted a considerable amount of attention in recent years and has been applied successfully in various fields of synthetic organic chemistry, proteins, peptides, drug discovery, and green chemistry. The various roles of microwaveassisted organic chemistry in green and sustainable chemistry are discussed, beginning with the strategies, technologies, and methods that were employed routinely at the time of the first reports of microwave applications. Microwave processing has several advantages over conventional sintering/heating, such as the reduction in cycle time, energy efficiency, eco-friendliness, and providing finer microstructures, leading to improved mechanical properties. Herein, we also describe the evolution of the microwave and some early applications of microwave assistance in the biomolecular sciences and treatment of solid malignant tumors.

Synthesis and biological activity of some new 1-benzyl and 1-benzoyl-3-heterocyclic indole derivativesStarting from 1-benzyl- (2a) and 1-benzoyl-3-bromoacetyl indoles (2b) new heterocyclic, 2-thioxoimidazolidine (4a, b), imidazolidine-2,4-dione (5a, b), pyrano(2,3-d)imida-zole (8a, band9a, b), 2-substituted quinoxaline (11a, b-17a, b) and triazolo(4,3-a)quinoxaline derivatives (18a, band19a, b) were synthesized and evaluated for their antimicrobial and anticancer activities. Antimicrobial activity screening performed with concentrations of 0.88, 0.44 and 0.22 μg mm-2showed that 3-(1-substituted indol-3-yl)quinoxalin-2(1H)ones (11a, b) and 2-(4-methyl piperazin-1-yl)-3-(1-substituted indol-3-yl) quinoxalines (15a, b) were the most active of all the tested compounds towardsP. aeruginosa, B. cereusandS. aureuscompared to the reference drugs cefotaxime and piperacillin, while 2-chloro-3-(1-substituted indol-3-yl)quinoxalines (12a, b) were the most active against C.albicanscompared to the reference drug nystatin. On the other hand, 2-chloro-3-(1-benzyl indol-3-yl) quinoxaline12adisplay potent efficacy against ovarian cancer xenografts in nude mice with tumor growth suppression of 100.0 ± 0.3 %.

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A straightforward synthesis of various nitrogenated heterocycles using a cyanoacetylating reagent from cyanoacetic acid and acetic anhydride is described. Biological testing of the synthesized compounds for their antibacterial and antifungal activities has been carried out.Heterocycles containing cyanoacetyl groups are relatively low explored; most of reported preparations were obtained either via nucleophilic displacement of halide atom in haloacetyl derivatives by cyanide [1] or from an alkyl carboxylate reacted with acetonitrile in presence of a strong base [2]. It was reported that cyanoacetic acid could serve as a building block in various reactions such as cyclization [3] and synthesis of coumarins [4] and other heterocycles [5]. The activation of cyanoacetic acid by conversion to a mixed anhydride with acetic anhydride was also used [6 -8], but the generality, simplicity and usefulness of this method was not appreciated and this reagent was rarely used for N-acetylation of, e.g., urea and C-acetylations of enamines [9]. Other activation procedures, such as conversions to cyanoacetyl chloride, have also been used, although this reagent is characterized by a tendency to self-polymerization, particularly when heated [7].Recently, we reported the use of cyanoacetic acid in the synthesis of simple nitrogenated heterocyclic compounds [10,11] to demonstrate the general applicability of cyanoacetic acid -acetic anhydride reagent. We have investigated its scope on selected simple nitrogenated compounds, namely, 2-imidazolidone (Ia) and thiosemicarbazide (Ib) to afford 3-oxo-3-(2-oxoimidazol-1-yl)propanenitrile (IIa) and 2-cyano-N-(5-methyl-1,3,4-thiadiazol-2-yl)acetamide (IIb) respectively, in good yields (Scheme 1). The structures of IIa and IIb were determined on the basis of analytical data. The IR spectrum of IIa revealed absorption bands at 1756, 1675 (2CO) , 3270 and 2260 cm -1 attributed to NH and CN groups, respectively, while its 1 H NMR spectrum showed, in addition to the two triplet signals (two protons each) of imidazolone CH 2 , a new singlet at ( = 4.30 ppm characteristic of CH 2 CN protons. In a similar manner, the IR spectrum of IIb showed absorptions bands at 3170 (NH), 2250 (CN) and 1690 (CO) cm -1 and its 1 H NMR spectrum displayed signals at ( = 2.70 (CH 3 ), 4.20 (CH 2 CN) and 12.75 ppm (exchangeable NH proton); in addition, the mass spectrum showed ion peak [M + ] at m/z = 182, which was in agreement with the calculated molecular weight (C 6 H 6 N 4 OS) (see the Experimental section).Compounds IIa and IIb can serve as building blocks in the synthesis of various nitrogenated bioactive molecules; thus, nitrosation of IIa and IIb using sodium nitrite afforded the corresponding hydroxyimino derivatives IIIa and IIIb, respectively. The 1 H NMR spectrum of IIIb as a representative example showed a signal due to hydroxyl proton (D 2 O exchangeable) at 10.92 ppm, instead of the CH 2 protons signal previously observed for the parent substance; in addition, the mass spectrum revealed ion peak [M + ] at ...

A series of Schiff bases bearing isoxazole and pyrazole rings were synthesized. Application of thioglycollic acid on two selective synthesized Schiff bases afforded the corresponding thiazolidin‐4‐one derivatives. On the other hand, following the multicomponents one‐pot Kabachnik– Fields reaction, the Schiff base generated in situ from 4‐chlorobenzaldehyde and 5‐methyl isoxazol‐3‐amine was trapped by phosphorus reagents to produce the corresponding amino phosphonates in moderate yields. However, the latter products could also be obtained in better yields (≥78%) by directly applying the dialkylphosphites to a selective synthesized Schiff base. Similarly, a series of α‐aminophosphonates could be obtained from 5‐chloro‐3‐methyl‐1H‐pyrazol‐4‐carbaldehyde, 5‐methylisoxazol‐3‐amine, and phosphorus reagents. Moreover, applying hexaalkyl triamido phosphites to the N‐(4‐chlorobenzylidene)‐5‐methylisoxazol‐3‐amine in ethanol afforded methylphosphonic diamide derivatives, whereas N‐((5‐chloro‐3‐methyl‐1H‐pyrazol‐4‐yl)methylene)‐5‐methylisoxazol‐3‐amine underwent dechlorination through reaction with hexaalkyl triamido phosphites to give the respective amine derivatives.