In this study, a multicomponent reaction involving carbohydrates, β-dicarbonyl compounds, and malononitrile was disclosed to synthesize a new class of polyhydroxy compounds incorporating pyrano[2,3- d ]pyrimidine, pyrido[2,3- d ]pyrimidine and chromene heterocycles under mild conditions. For the synthesis of this class of compounds, glucose, galactose, arabinose, maltose, and lactose were used as aldehyde component in the reaction with barbituric acid and malononitrile to produce pyrano[2,3- d ]pyrimidine derivatives. By use of 1,3-cyclohexanedione instead of barbituric acid, chromene derivatives incorporating carbohydrate moieties were obtained. Also, the four-component condensation reaction between d -glucosamine, aldehyde, malononitrile, and barbituric acid was efficiently provided polyhydroxy-substituted pyrido[2,3- d ]pyrimidine derivatives. This new combinatorial approach gave a range of carbohydrate-derived heterocycles in good to excellent yields with high potential biological applications. The antioxidant activities were evaluated using 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) antioxidant measuring system, and the data were expressed as Trolox equivalent antioxidant capacity. All of these compounds display significant antioxidant activity. The maximum and minimum antioxidant activities were observed for 4j and 6b , respectively. Our results indicated encouraging perspectives for the improvement and usage of this type of synthetic compounds, indicating significant levels of antioxidant activity.

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The development of resistance and unwanted harmful interaction with other biomolecules instead of DNA are the major drawbacks for application of platinum (Pt) complexes in cancer chemotherapy. To conquer these problems, much works have been done so far to discover innovative Pt complexes. The objective of the current study was to evaluate the anti cancer activities of a series of four and five-coordinated Pt(II) complexes, having deprotonated 2-phenyl pyridine (abbreviated as C^N), biphosphine moieties, i.e., dppm = bis(diphenylphosphino) methane (Ph(2)PCH(2)PPh(2)) and dppa = bis(diphenylphosphino)amine (Ph(2)PNHPPh(2)), as the non-leaving carrier groups. The growth inhibitory effect of the Pt complexes [Pt(C^N)(dppm)]PF(6): C(1), [Pt(C^N)(dppa)]PF(6): C(2), and [Pt(C^N)I(dppa)]: C(3), toward the cancer cell lines was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In addition, the florescence quenching experiments of the interaction between human serum albumin (HSA) and the Pt complexes were performed in order to obtain the binding parameters and to evaluate the denaturing properties of these complexes upon binding to the general carrier protein of blood stream. The structure-activity relationship studies reveal that four-coordinated Pt complexes C(1) and C(2) with both significant hydrophobic and charge characteristics, not only exhibit strong antiproliferation activity toward the cancer cell lines, but also they display lower denaturing effect against carrier protein HSA. On the other hand, five-coordinated C(3) complex with the unusual intermolecular NH…Pt hydrogen binding and the intrinsic ability for oligomerization, exhibits poor anticancer activity and strong denaturing property. The current study reveals that the balance between charge and hydrophobicity of the Pt complexes, also their hydrogen binding abilities and coordination mode are important for their anticancer activities. Moreover, this study may suggest C(1) and C(2) as the potential template structures for synthesis of new generation of four-coordinated Pt complexes with strong anticancer activities and weak denaturing effects against proteins.

Diabetes mellitus is a metabolic disorder characterized by high blood glucose levels and instability in carbohydrate metabolism. For treating diabetes, one important therapeutic approach is reducing the postprandial hyperglycemia which can be managed by delaying the absorption of glucose through inhibition of the carbohydrate-hydrolyzing enzymes, α-amylase (α-Amy) and αglucosidase (α-Gls) in the digestive tract. In this work, a new class of curcumin derivatives incorporating pyrano[2,3-d]pyrimidine heterocycles was synthesized using a multicomponent reaction between curcumin, aldehydes, and barbituric acid. Using UV-Vis spectroscopic method, the synthetic compounds were assessed for their inhibitory properties against α-Amy and α-Gls enzymes. Also, the antioxidant potential of these compounds was measured spectroscopically and compared with Trolox which is known as a gold standard to measure antioxidant capacity. The results of present study suggest that the curcumin derivatives were able to efficiently inhibit both yeast and mammalian α-Gls. In comparison with the antidiabetic medicine acarbose, the synthetic curcumin derivatives were also capable to inhibit more effectively the yeast α-Gls. The partial inhibitory effects of these compounds against pancreatic α-Amy were also important in the terms of avoiding development of the possible gastrointestinal side effects. Moreover, some of the curcumin derivatives indicated stronger antioxidant activity than Trolox. Overall, these synthetic curcumin analogues might be considered as novel molecular templates for development of efficient antidiabetic compounds with promising inhibitory activities against α-Amy and α-Gls enzymes.

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