Synthesis and pharmacological activity of 4-(4'-(chlorophenyl)-4-hydroxypiperidine) derivatives

A new series of 4-(4'-chlorophenyl)-4-hydroxypiperidine derivatives (2-5), substituted at nitrogen, were synthesized and tested as potential analgesic compounds as well as evaluated for their effect on hypotensive activity. Results showed that all the derivatives exhibit significant analgesic activity in male Wistar rats at a dose of 50 mg/kg of body weight after intramuscular injection, when tested by thermal stimuli (tail flick test). Pethidine was used as reference drug. Compounds 2, 3 and 5 produced reduction in blood pressure in normotensive rat.     

Design,Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis

Small molecules with nitrogen-containing scaffolds have gained much attention due to their biological importance in the development of new anticancer agents. The present paper reports the synthesis of a library of new dihydropyridine and pyridine analogs with diverse pharmacophores. All compounds were tested against the human tissue nonspecific alkaline phosphatase (h-TNAP) enzyme. Most of the compounds showed excellent enzyme inhibition against h-TNAP, having IC₅₀ values ranging from 0.49 ± 0.025 to 8.8 ± 0.53 µM, which is multi-fold higher than that of the standard inhibitor (levamisole = 22.65 ± 1.60 µM) of the h-TNAP enzyme. Furthermore, an MTT assay was carried out to evaluate cytotoxicity against the HeLa and MCF-7 cancer cell lines. Among the analogs, the most potent dihydropyridine-based compound 4d was selected to investigate pro-apoptotic behavior. The further analysis demonstrated that compound 4d played a significant role in inducing apoptosis through multiple mechanisms, including overproduction of reactive oxygen species, mitochondrial dysfunction, DNA damaging, and arrest of the cell cycle at the G1 phase by inhibiting CDK4/6. The apoptosis-inducing effect of compound 4d was studied through staining agents, microscopic, and flow cytometry techniques. Detailed structure–activity relationship (SAR) and molecular docking studies were carried out to identify the core structural features responsible for inhibiting the enzymatic activity of the h-TNAP enzyme. Moreover, fluorescence emission studies corroborated the binding interaction of compound 4d with DNA through a fluorescence titration experiment.     

Synthesis of 2-Aminopyrimidine Derivatives and Their Evaluation as β-Glucuronidase Inhibitors: In Vitro and In Silico Studies

Currently the discovery and development of potent β-glucuronidase inhibitors is an active area of research due to the observation that increased activity of this enzyme is associated with many pathological conditions, such as colon cancer, renal diseases, and infections of the urinary tract. In this study, twenty-seven 2-aminopyrimidine derivatives 1–27 were synthesized by fusion of 2-amino-4,6-dichloropyrimidine with a variety of amines in the presence of triethylamine without using any solvent and catalyst, in good to excellent yields. All synthesized compounds were characterized by EI-MS, HREI-MS and NMR spectroscopy. Compounds 1–27 were then evaluated for their β-glucuronidase inhibitory activity, and among them, compound 24 (IC₅₀ = 2.8 ± 0.10 µM) showed an activity much superior to standard D-saccharic acid 1,4-lactone (IC₅₀ = 45.75 ± 2.16 µM). To predict the binding mode of the substrate and β-glucuronidase, in silico study was performed. Conclusively, this study has identified a potent β-glucuronidase inhibitor that deserves to be further studied for the development of pharmaceutical products.     

Trichosides A and B,new withanolide glucosides from Tricholepis eburnea

Trichosides A (1) and B (2), new withanolide glucosides, have been isolated from the n-butanolic fraction of the 75% methanolic extract of aerial parts of Tricholepis eburnea. Their structures were elucidated through spectroscopic analysis including ESI-MS, 2D NMR and acid hydrolysis.     

Ailanthus altissima (Miller) Swingle fruit - new acyl β-sitosteryl glucoside and in vitro pharmacological evaluation

β-Sitosterol-3-O-(6?-O-13?-octadecenoyl)-β-D-glucoside (1), a new acyl β-sitosteryl glucoside, along with three known compounds β-sitosterol-3-O-β-D-glucoside (2), β-sitosterol (3) and methyl gallate (4) have been isolated from the ethyl acetate soluble fraction of methanolic extract of Ailanthus altissima fruits. Their structures were elucidated through spectroscopic data including 2D NMR, ESI-MS, methanolysis and oxidative cleavage of double bond. Antibacterial, antifungal, cytotoxic, phytotoxic and insecticidal activities were evaluated of compound 1, crude extract and its fractions so far for the first time. Pharmacological activities results showed that n-butanol fraction was good active against Pseudomonas aeruginosa and Salmonella typhi bacteria, and moderate active against Microsporum canis fungus. Crude extract, n-butanol and aqueous fractions showed good cytotoxicity. Moreover, compound 1, extract and all fractions showed notable phytotoxicity at higher concentrations, whereas all inactive against assayed insects.     

He-Ne laser-induced improvement in biochemical, physiological, growth and yield characteristics in sunflower (Helianthus annuus L.)

The water-soaked seeds of sunflower were exposed to low power continuous wave He-Ne laser irradiation of energies 0, 100, 300 and 500 mJ to evaluate the effect on various biochemical, physiological, growth and yield parameters of sunflower. The experiments which consisted of four replicates arranged in a completely randomized design (CRD) were carried out under the greenhouse conditions. The physiological attributes like, photosynthetic rate (A), transpiration rate (E), intrinsic CO(2) concentration (C(i) ), stomatal conductance (g(s)), chlorophyll a and b contents, relative membrane permeability and leaf water (ψ(w)), osmotic (ψ(s)) and turgor (ψ(p)) potentials, relative water contents and leaf area increased significantly as compared to control due to He-Ne treatment of seeds. The activities of superoxide dismutase, peroxidase and catalases and contents of total soluble proteins, malondialdehyde, proline and leaf total phenolic also increased due to laser treatment. Significant increase in growth parameters of sunflower like shoot fresh and dry masses, root fresh and dry masses, root and shoot lengths, number of leaves per plant and stem diameter has also been observed. The contents of K, Ca and Mg in shoot and root were also increased and an overall increase of up to 28.12% was observed due to laser treatment.     

Transfer of radioactivity from soil to vegetation in Rechna Doab, Pakistan

In Rechna Doab, samples of the most common vegetation, perennial grass Desmostachya bipinnata (dab), were collected along with soil samples from 29 sites. Natural radioactivity of 22?Ra, 232Th/22?Ac and ??K was measured by using high purity germanium-based gamma ray spectrometer. Activity concentration levels of 22?Ra, 232Th/22?Ac and ??K in soil were found to be 46.8 ± 6.2 (36.0-57.6), 61.4 ± 5.9 (48.2-73.2) and 644.8 ± 73.9 (537.7-868.4) Bq kg?1 (dry mass), respectively, and those in vegetation were 2.74 ± 1.70 (1.00-6.39), 2.24 ± 0.59 (1.56-2.61) and 172.72±113.37 (53.14-469.24) Bq kg?1 (dry mass), respectively. The measured values of the activity concentration in vegetation are comparable with some other international data. Calculated soil to vegetation transfer factors of 22?Ra, 22?Ac and ??K were 0.06 ± 0.03 (0.02-0.14), 0.04 ± 0.01 (0.03-0.04) and 0.26 ± 0.16 (0.09-0.69). The mean outdoor absorbed dose rate in air for the area under study was determined as 8.22 nGy h?1 and the mean indoor absorbed dose rate in air was 11.52 nGy h?1. The total annual effective dose to the general public from the vegetation was found to be (0.02-0.16) mSv, which is below the recommended limit value of 1 mSv y?1 for the general public. The dab vegetation under study was found to be radiologically safe for the population and environment.     

Transfer of radioactivity from soil to vegetation in Rechna Doab,Pakistan

In Rechna Doab, samples of the most common vegetation, perennial grass Desmostachya bipinnata (dab), were collected along with soil samples from 29 sites. Natural radioactivity of ²²⁶Ra, ²³²Th/²²⁸Ac and ⁴⁰K was measured by using high purity germanium-based gamma ray spectrometer. Activity concentration levels of ²²⁶Ra, ²³²Th/²²⁸Ac and ⁴⁰K in soil were found to be 46.8±6.2 (36.0–57.6), 61.4±5.9 (48.2–73.2) and 644.8±73.9 (537.7–868.4) Bq kg^?1 (dry mass), respectively, and those in vegetation were 2.74±1.70 (1.00–6.39), 2.24±0.59 (1.56–2.61) and 172.72±113.37 (53.14–469.24) Bq kg^?1 (dry mass), respectively. The measured values of the activity concentration in vegetation are comparable with some other international data. Calculated soil to vegetation transfer factors of ²²⁶Ra, ²²⁸Ac and ⁴⁰K were 0.06±0.03 (0.02–0.14), 0.04±0.01 (0.03–0.04) and 0.26±0.16 (0.09–0.69). The mean outdoor absorbed dose rate in air for the area under study was determined as 8.22 nGy h^?1 and the mean indoor absorbed dose rate in air was 11.52 nGy h^?1. The total annual effective dose to the general public from the vegetation was found to be (0.02–0.16) mSv, which is below the recommended limit value of 1 mSv y^?1 for the general public. The dab vegetation under study was found to be radiologically safe for the population and environment.     

Relations between kinetic parameters of different column models for liquid chromatography applying core-shell particles

This article presents analytical solutions of the general rate model (GRM), the lumped kinetic model (LKM), and the simpler equilibrium dispersive model (EDM) for core-shell particles and linear adsorption isotherms. The solutions in the Laplace domain are applied to derive analytical expressions for the temporal moments of these models. The results provide relations between the model specific kinetic parameters by matching one or more of the temporal moments. Several case studies are considered for illustration. The results show that simpler models are in many cases as good as the most detailed GRM if their kinetic parameters fulfill the matching relations. Thus, it is possible to reliably predict elution profiles using the simpler models. The derived analytical expressions can also be utilized to efficiently estimate model parameters from experimentally observed elution profiles to further optimize core-shell particles and to identify suitable column sizes and operating conditions.