Samreen Saleem

Plants Fagonia cretica L. and Hedera nepalensis K. Koch contain natural compounds with potent dipeptidyl peptidase-4 (DPP-4) inhibitory activity

ETHNOPHARMACOLOGICAL RELEVANCE The two plants investigated here (Fagonia cretica L. and Hedera nepalensis K. Koch) have been previously reported as natural folk medicines for the treatment of diabetes but until now no scientific investigation of potential anti-diabetic effects has been reported. MATERIALS AND METHODS In vitro inhibitory effect of the two tested plants and their five isolated compounds on the dipeptidyl peptidase 4 (DPP-4) was studied for the assessment of anti-diabetic activity. RESULTS A crude extract of Fagonia cretica possessed good inhibitory activity (IC₅₀ value: 38.1 μg/ml) which was also present in its n-hexane (FCN), ethyl acetate (FCE) or aqueous (FCA) fractions. A crude extract of Hedera nepalensis (HNC) possessed even higher inhibitory activity (IC50 value: 17.2 μg/ml) and this activity was largely retained when further fractionated in either ethyl acetate (HNE; IC50: 34.4 μg/ml) or n-hexane (HNN; 34.2 μg/ml). Bioactivity guided isolation led to the identification of four known compounds (isolated for the first time) from Fagonia cretica: quinovic acid (1), quinovic acid-3β-O-β-D-glycopyranoside (2), quinovic acid-3β-O-β-D-glucopyranosyl-(28→1)-β-D-glucopyranosyl ester (3), and stigmasterol (4) all of which inhibited DPP-4 activity (IC₅₀: 30.7, 57.9, 23.5 and >100 µM, respectively). The fifth DPP-4 inhibitor, the triterpenoid lupeol (5) was identified in Hedera nepalensis (IC₅₀: 31.6 μM). CONCLUSION The experimental study revealed that Fagonia cretica and Hedera nepalensis contain compounds with significant DPP-4 inhibitory activity which should be further investigated for their anti-diabetic potential.

Electrochemical and spectroscopic investigations of carboxylic acid ligand and its triorganotin complexes for their binding with ds.DNA: in vitro biological studies.

A carboxylic acid ligand, (Z)-4-(4-acetylphenylamino)-4-oxobut-2-enoic acid (APA-1), and its triphenyl-(APA-2) and tributyl-tin(IV) (APA-3) compounds have been synthesized and investigated for their binding with ds.DNA using UV-visible spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and viscosity measurements under physiological conditions of pH and temperature. The experimental results from all techniques i.e. binding constant (Kb), binding site size (n) and free energy change (ΔG) were in good agreement and inferred spontaneous compound-DNA complexes formation via intercalation. Among all the compounds APA-3 showed comparatively greater binding at pH 4.7 as evident from its greater Kb values {APA-3: Kb: 5.63×10(4)M(-1) (UV); 7.94×10(4)M(-1) (fluorescence); 9.91×10(4)M(-1) (CV)}. Electrochemical processes of compounds before and after the addition of DNA were found diffusion controlled. Among all compounds, APA-3 exhibited best antitumor activity.

Naturally-occurring TGR5 agonists modulating glucagon-like peptide-1 biosynthesis and secretion

Selective GLP-1 secretagogues represent a novel potential therapy for type 2 diabetes mellitus. This study examined the GLP-1 secretory activity of the ethnomedicinal plant, Fagonia cretica, which is postulated to possess anti-diabetic activity. After extraction and fractionation extracts and purified compounds were tested for GLP-1 and GIP secretory activity in pGIP/neo STC-1 cells. Intracellular levels of incretin hormones and their gene expression were also determined. Crude F. cretica extracts stimulated both GLP-1 and GIP secretion, increased cellular hormone content, and upregulated gene expression of proglucagon, GIP and prohormone convertase. However, ethyl acetate partitioning significantly enriched GLP-1 secretory activity and this fraction underwent bioactivity-guided fractionation. Three isolated compounds were potent and selective GLP-1 secretagogues: quinovic acid (QA) and two QA derivatives, QA-3β-O-β-D-glycopyranoside and QA-3β-O-β-D-glucopyranosyl-(28→1)-β-D-glucopyranosyl ester. All QA compounds activated the TGR5 receptor and increased intracellular incretin levels and gene expression. QA derivatives were more potent GLP-1 secretagogues than QA. This is the first time that QA and its naturally-occurring derivatives have been shown to activate TGR5 and stimulate GLP-1 secretion. These data provide a plausible mechanism for the ethnomedicinal use of F. cretica and may assist in the ongoing development of selective GLP-1 agonists.

Synthesis, characterization, and biological activity of transition metals complexes with mefenamic acid (NSAIDs)

A new series of transition metal complexes have been synthesized with [(2,3-dimethylphenyl)-amino]benzoic acid (Mefenamic acid) in 1 : 1/1 : 2 M : L ratio. The complexes have been characterized by elemental analysis, FT-IR and UV-Vis spectroscopy. Antifungal, antibacterial, antitumor, antioxidant (DPPH, H2O2 induced DNA damage) activity of the complexes and DNA interaction with the complexes were studied. The results revealed that the ligand and most of synthesized compounds did not demonstrate significant antibacterial activity unlike [Ni(Mef)(H2O)Cl] that exhibited pronounced activity against F. Solani. Antitumor activity of the products was higher than that of the free ligand.

UV-absorption studies of interaction of karanjin and karanjachromene with ds. DNA: Evaluation of binding and antioxidant activity

AbstractTwo flavonoids, karanjin (Kj) and karanjachromene (Kc) have been investigated spectrophotometrically for their mode of interactions with double stranded (ds)-DNA at blood (7.4) and stomach (4.7) pH and at human body temperature (37°C). Benesi-Hildebrand equation was used to evaluate the binding constants, Kb. Binding constants at both pH values and at body temperature showed stronger binding of both the flavonoids and formation of 1:1 flavonoid-DNA complex via intercalative mode. However, Kb values for karanjin were evaluated to be comparatively greater than karanjachromene at both pH values. The highest value of binding constant (1.32×105 M−1) for karanjin at blood pH (7.4) demonstrated its comparatively stronger binding and greater effectiveness at this pH. Standard Gibbs free energy changes (ΔG) of flavonoid-DNA complexes were calculated as negative values and indicative of spontaneity of their binding. Both flavonoids showed significant DNA protection activity.

Hedera nepalensis K. Koch: A Novel Source of Natural Cancer Chemopreventive and Anticancerous Compounds.

Traditional medicinal plants are often used for both the prevention and the treatment of local diseases. Taking into consideration the medicinal importance of Hedera nepalensis within local Pakistani traditions, the present study was undertaken to analyze the in vitro cancer chemopreventive and cytotoxic properties of the plant. The in vitro cancer chemopreventive testing was performed using nitrite assay, NFκB assay, aromatase assay, and quinone reductase 1 (QR1) assay. The cytotoxic potential was evaluated on three cancer‐cell lines: MCF‐7, MDA‐MB‐231, and HeLa using sulforhodamine B (SRB) assay. The results of cancer chemopreventive assays show that n‐hexane and ethyl acetate fractions of tested plant have promising cancer chemopreventive potential. Lupeol isolated from n‐hexane as well as ethyl acetate fraction showed lowest IC50 (0.20 ± 1.9 μM) in NFκB assay. Crude extract and its fractions inhibited the growth of three cancer cell lines by more than 60%, IC50 value of lupeol varied from 2.32 to 10.2 μM. HPLC‐DAD‐based quantification of lupeol in different plant tissues demonstrated that leaves of H. nepalensis are a rich source of lupeol (0.196 mg/100 mg dry weight). Our data have shown that H. nepalensis harbors cancer chemopreventive and cytotoxic agents. Copyright

Synthesis, Characterization and Thermal Studies of Transition Metal Complexes with O-, S-Donor Ligands

Transition metal carboxylates have been synthesized with transition metal chlorides of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II) and Ru(III). The binding ligands are 3-[(4-bromophenylamido)]propenoic acid (L) and diethyl dithiocarbamate. All these compounds have been characterized by elemental analyses, conductivity measurements, UV/Vis, FT-IR spectroscopy and thermal analysis. Semi empirical studies of three compounds have also been carried out for structural elucidation showing that the Cr and Co derivatives have a six coordinated octahedral geometry which is in accordance with the data obtained from elemental analysis, UV/visible and FTIR spectroscopy. Thermal studies of all synthesized derivatives were carried out in a temperature range of 50-1000°C under inert atmosphere. Their kinetic parameters, like activation energy, enthalpy, entropy and order of reaction, were also studied. All complexes decompose at a certain temperature leaving behind metal oxides as residual products. The synthesized complexes showed remarkable anti-bacterial activities with a few exceptions. Selected compounds were also investigated for DNA damage assay. The interaction of selected metal derivatives with DNA and their binding strength were investigated by UV/vis spectroscopy. The increasing order is [CuL(H2O)2]Cl < [RuLL’(H2O)2]Cl < [FeL(H2O)4]Cl2 < [CuLL’ < 3-[(4-bromophenylamido)] propenoic acid.