Ferrocenyl,Alkyl, and Aryl‐Pyrido[2,3‐d]Pyrimidines as Vasorelaxant of Smooth Muscle of Rat Aorta via cAMP Conservation Through Phosphodiesterase Inhibition

New pyrido[2,3‐d]pyrimidines 11 , 12 , 13 , and 21 have been synthesized. The vasorelaxant effect on smooth muscle isolated from rat aorta, via PDEs inhibition, of these compounds along with other pyrido[2,3‐d]pyrimidines 14 , 15 , 16 , 17 , 18 , 19 , 20 reported earlier by our group, has also been determined. These pyrido[2,3‐d]pyrimidines 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 were synthesized by the reaction of ferrocenyl‐ethynyl ketones ( 1 , 2 , 3 , 4 ) or α‐alkynyl ketones ( 5 , 6 , 7 , 8 , 9 , 10 ) with 6‐amino‐1,3‐dimethyluracil using [Ni(CN)₄]^?4 as an active catalytic species, formed in situ in a Ni(CN)₂/NaOH/H₂O/CO/KCN aqueous system. Evaluation of the vasorelaxant effect of compounds 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 demonstrated that all compounds relax the tissue in a concentration‐dependent manner. The structural changes do not alter the effectiveness; however, there are differences related to potency expressed as EC₅₀. Compounds 12 (7‐ferrocenyl‐1,3‐dimethyl‐5‐(m‐tolyl)‐pyrido[2,3‐d]pyrimidine) and 13 (7‐ferrocenyl‐1,3‐dipropyl‐5‐(4‐metoxyphenyl)‐pyrido[2,3‐d]pyrimidine) were the most potent compounds, even more than rolipram, reference drug; the EC₅₀ was 0.41 ± 0.02 μM and 0.81 ± 0.11 μM for 12 and 13 , correspondingly. The EC₅₀ of compounds 15 (7‐ferrocenyl‐1,3‐dimethyl‐5‐phenyl‐pyrido[2,3‐d]pyrimidine), 14 (7‐ferrocenyl‐5‐(3,5‐dimethoxyphenyl)‐1,3‐dimethylpyrido[2,3‐d]pyrimidine), and 19 (5‐n‐butyl‐7‐ethyl‐1,3‐dimethylpyrido[2,3‐d]pyrimidine) was similar to EC₅₀ of rolipram. Compounds 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 significantly induce concentration‐dependent vasorelaxation in endothelium‐intact aortic rings. In addition, the relaxation responses to each compound in either endothelium‐intact or endothelium denuded aortic rings were comparable, suggesting that removal of the functional endothelium has no significant influence on its intrinsic vasorelaxant activity. In vitro capability of conserving cyclic‐AMP or cyclic‐GMP (adenosine and guanosine 3′, 5′‐cyclic monophosphate) via PDE inhibition for compounds 12 , 13 , 14 , 15 and 19 was evaluated. Compounds 15 and 19 show the highest percent inhibition effect (94.83% and 83.98%, respectively) for the decomposition of c‐AMP. Docking studies showed that the compound 15 was selective for the inhibition of PDE‐4.     

Synthesis and Cytotoxicity Evaluation of Novel Andrographolide‐1,2,3‐Triazole Derivatives

A series of new andrographolide‐1,2,3‐triazole derivatives, 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , were synthesized from a natural bioactive labdane type diterpenoid, andrographolide. All the derivatives were screened against human cancer cell lines MCF7, MDA‐MB‐231, COLO205, HepG2, K562, Hela, and HEK293 to evaluate their cytotoxic activity. All the compounds showed anticancer activity selectively against K562 cell line, with IC₅₀ values ranging from 8.00 to 17.11 µM, and are inactive against the rest of the cell lines. Compounds 3c and 3d showed significant cytotoxicity among the synthesized derivatives. The in silico docking studies revealed compounds 3b and 3d with high binding affinity against the cancer target, transient receptor potential vanilloid 1.     

Enhanced thermal properties of highly monodispersed ZnO nanoparticle/poly(styrene-<Emphasis Type="Italic">co</Emphasis>-acrylonitrile) nanocomposite

Chemical based approach for the synthesis of poly(styrene-co-acrylonitrile)/ZnO nanocomposites with different ZnO nanoparticle content by in situ emulsion polymerization is discussed. A significant increase in the thermal degradation temperature, melting and crystallization temperatures in all nanocomposite is observed. Increasing ZnO loading to polymer matrix enhances the flame retardant ability of polymer matrix with an appreciable increase in thermal degradation temperature of pristine polymer.     

β‐Alkyloxazolochlorins: Revisiting the Ozonation of Octaalkylporphyrins,and Beyond

The reaction of β‐octaalkylporphyrins (octaethylporphyrin and etioporphyrin I) with ozone generated the corresponding heptaalkyloxazolochlorinhemiacetals in which a pyrrolic subunit of the porphyrins was replaced by an oxazoline moiety. Thus, a pyrrolic β‐carbon with its alkyl substituent was excised and replaced by an oxygen atom, and the neighboring β‐carbon was hydroxylated. This work clarifies the nature of the products first described by Fischer and De?eli?, in 1933, and verifies the work by Shulg′a and coworkers, from 1977. Furthermore, the chemistry of the oxazolochlorin hemiacetals was studied: They could be dehydroxylated or converted to alkyl acetals and gem‐dialkyl derivatives, all possessing chlorin‐type optical spectra. Their oxidative conversions generated a unique tetrahydrofuran‐linked oxazolochlorin dimer and a hexaethylporpholactone. The work expands on the knowledge of converting porphyrins to porphyrinoids of potential utility containing nonpyrrolic building heterocycles.     

Insecticidal activity of a novel fatty acid amide derivative from Streptomyces species against Helicoverpa armigera

Helicoverpa armigera, an important pest causes serious damage to grain legumes. The main objective of this study was to isolate and identify the metabolite against H. armigera from a previously characterised Streptomyces sp. CAI-155. The culture filtrate of CAI-155 was extracted using Diaion HP-20 and the active fractions were fractionated on Silica and C18 column chromatography. The C18 active fraction was further fractionated on Silica gel 60 F₂₅₄ thin layer chromatography (TLC). The most active fraction (Rf 0.64) purified from TLC led to the identification of a novel metabolite N-(1-(2,2-dimethyl-5-undecyl-1,3-dioxolan-4-yl)-2-hydroxyethyl)stearamide by spectral studies. The purified metabolite showed 70–78% mortality in 2nd instar H. armigera by diet impregnation assay, detached leaf assay and greenhouse assay. The LD₅₀ and LD₉₀ values of the purified metabolite were 627 and 2276 ppm, respectively. Hence, this novel metabolite can be exploited for pest management in future.     

Mesomorphism of azo-esters and chalcone-esters

One chalcone-ester homologous series of mesogens α-4-[4^/-n-alkoxybenzoyloxy phenyl β-4^//methoxy benzoyl ethylenes (A) and one azo-ester homologous series of mesogens p-(p^/-n-alkoxybenzoyloxy) phenyl azo-p^//-methoxy benzene (B) being structurally similar are discussed. Both series (A) and (B) differ in respect of central bridges linking two phenyl rings. Mesomorphic properties start from 6th and 1st member of series (A) and (B) respectively. In series (A), 6th to 12th members show both smectogenic and nematogenic properties, and the 14th and 16th members show only nematogenic property. While in series (B), 1st to 10th members show nematogenic properties, 11th member shows both smectogenic and nematogenic properties, while 12th member shows only smectogenic property. Thermal stability of series (A) is relatively high as compared to series (B). Transition temperatures are observed through hot stage polarizing microscope by the miscibility method. Analytical data support the structure of molecules. Textures of series (A) in nematic are threaded and Schlieren in SmecticSmectic A type, while that of series (B) in nematic are threaded in SmecticSmectic A and smectic C.     

X-ray crystallography of methyl (6-amino-5-cyano-2-methyl-4-(2-nitrophenyl)-4<Emphasis Type="Italic">H</Emphasis>-pyran)-3-carboxylate

The organic carbonitrile namely methyl (6-amino-5-cyano-2-methyl-4-(2-nitrophenyl)-4H-pyran)- 3-carboxylate is synthesized via one-pot multi-component reaction at room temperature using commercially available urea as inexpensive and environmentally benign organo-catalyst and its crystal structure is determined by X-ray technique. The crystals are monoclinic, sp. gr. C2/c, a = 12.3069(8) Å, b = 9.7023(7) Å, c = 24.812(2) Å, β = 94.862(6)°, Z = 8. The dihedral angle between pyran and phenyl rings is 87.8(1)°; the pyran ring is almost planar The dihedral angle between the mean planes of phenyl ring and nitro group is 44.4(2)°. The crystal structure is stabilized by N?H···N and N?H···O hydrogen bonds. In addition, C?H···π interactions are also observed in the crystal structure.     

Finite element Galerkin approximations to a class of nonlinear and nonlocal parabolic problems

In this article, a finite element Galerkin method is applied to a general class of nonlinear and nonlocal parabolic problems. Based on an exponential weight function, new a priori bounds which are valid for uniform in time are derived. As a result, existence of an attractor is proved for the problem with nonhomogeneous right hand side which is independent of time. In particular, when the forcing function is zero or decays exponentially, it is shown that solution has exponential decay property which improves even earlier results in one dimensional problems. For the semidiscrete method, global existence of a unique discrete solution is derived and it is shown that the discrete problem has an attractor. Moreover, optimal error estimates are derived in both and ‐norms with later estimate is a new result in this context. For completely discrete scheme, backward Euler method with its linearized version is discussed and existence of a unique discrete solution is established. Further, optimal estimates in ‐norm are proved for fully discrete schemes. Finally, several numerical experiments are conducted to confirm our theoretical findings. © 2016 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 32: 1232–1264, 2016