Multicomponent access to novel proline/cyclized cysteine tethered monastrol conjugates as potential anticancer agents

The versatility of multicomponent Biginelli’s reaction is exploited in the development of proline and cyclized cysteine tethered conjugates of monastrol, a kinesin Eg5 inhibitor. Ten new conjugates are synthesized focusing on structural replacement of the ester moiety (C-5 position) of the monastrol backbone with amino acid based amide moieties. On cytotoxic evaluation, conjugate 24 has shown promising in vitro cytotoxic activity against leukemia. Molecular docking studies revealed that the conjugates 19 and 24 exhibit better interaction at kinesin Eg5 receptor compared to monastrol. Moreover, computational calculations and predictions of important molecular properties suggest that these new amino acid based conjugates could be further improved to provide potential anticancer agents.     

Unsymmetrically substituted benzimidazolium based Silver(I)-N-heterocyclic carbene complexes: Synthesis,characterization and in vitro anticancer study against human breast cancer and colon cancer

The promising biomedical applications of silver complexes stimulated the researchers to test these compounds against cancer. The present research work was designed to achieve this goal. In this work, a series of 5-methyl benzimidazole based N-Heterocyclic carbene ligands and respective silver(I) complexes were synthesized and tested on cancer cell lines to assess their anticancer activity. Unsymmetrically substituted benzimidazole was found unique in its reactivity and generation of a single product during NHC ligand formation was only possible after two successive alkylations with same alkyl halide. The corresponding Ag(I)-NHC adducts were obtained by in situ deprotonation of the NHC ligands. Synthesized compounds were characterized by various physcio-chemical and spectroscopic methods. Single crystal X-ray diffraction study of complex 7 revealed its mononuclear structure. Preliminary in vitro anticancer study of azolium salts and respective Ag(I)-NHC complexes against human breast cancer (MDA-MB-231), colon cancer (HCT-116) and normal endothelial cells (EA.hy926) cells revealed that all the compounds are more cytotoxic to cancer cells than normal cells and the complexes are relatively more potent compared to the corresponding NHC ligands. It was found that increased chain length and presence of methyl substituent on benzimidazole ring enhance the biopotency of Ag(I)-NHC complexes. The synthesized compounds were further studied for pro-apoptotic mechanism of action via Rhodamine 123 test. The tested compounds were found to induce apoptosis via extrinsic mitochondrial pathway.     

Oxovanadium(IV) and ruthenium(II) carbonyl complexes of ONS‐donor ligands derived from dehydroacetic acid and dithiocarbazate: Synthesis,characterization, antioxidant activity,DNA binding and in vitro cytotoxicity

A series of new complexes of oxovanadium(IV) [VO(L)(B)] and ruthenium(II) [Ru(CO)(PPh₃)₂(L)] ( 1.1- 1.3,  2.1–2.3 ) (H₂L = dehydroacetic acid Schiff base of S‐methyldithiocarbazate, H₂smdha ( 1 ) or S‐benzyldithiocarbazate, H₂sbdha ( 2 ); B = 2,2′‐bipyridine (bpy) or 1,10‐phenanthroline (phen)) have been synthesized. The structure of these complexes was authenticated using elemental analyses and spectroscopic techniques, and their magnetic properties and electrochemical behaviour were studied. The molecular structures of oxovanadium(IV) complexes [VO(smdha)(bpy)]?CH₂Cl₂ ( 1.1 ) and [VO(sbdha)(phen)]?2H₂O ( 2.2 ) were confirmed using single‐crystal X‐ray crystallography. Analytical data showed that the ligands 1 and 2 are chelated to the metal centres in a bi‐negative tridentate fashion through azomethine N, thiol S and deprotonated hydroxyl group. The antioxidant activity of the synthesized compounds was tested against 2,2‐diphenyl‐1‐picrylhydrazyl) radical, which showed that the complexes demonstrate a better scavenging activity than their corresponding ligands. The cupric ion reducing antioxidant capacity method was also employed and the total equivalent antioxidant capacity values were found to be higher for the oxovandium(IV) complexes. DNA binding affinity of the compounds was determined using UV–visible and fluorescence spectra, revealing an intercalation binding mode. Higher cytotoxicity for the complexes compared to their ligands was found against human liver hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF7) cell lines using MTT assay.     

Carbon‐based Nanosensors for Salicylate Determination in Pharmaceutical Preparations

Thiourea derivative‐based carbon paste electrode (TUD1‐CPE) was constructed as a potentiometric sensor for the determination of salicylate anion in pharmaceutical formulations, Aspocid® and Aspirin®. The optimized CPE contained 45.5 % graphite, 0.5 % reduced graphene oxide (rGO), 46.0 % nitrophenyl octyl ether (NPOE) plasticizer, 5.0 % TUD1 ionophore, and 3.0 % tridodecylmethyl ammonium chloride as additive. The incorporation of NPOE of high dielectric constant, and rGO in electrode caused better performance of the sensor; Nernstian response of 59.0 mV decade^?1 in the concentration range of 10^?1–10^?5 mole L^?1, a detection limit of 1×10^?5 mole L^?1 in a very short response time of 6 seconds. The prepared sensor showed high selectivity against similar anions (i. e. , benzoate, I^?, SCN^?). Selectivity was confirmed by calculating the formation constant (K_β) using sandwich membrane method, where K_β for TUD1‐salicylate is 10^0.43. Theoretical calculations at DFT‐B3LY/6‐31G** level of theory were performed to find interaction mechanism, Energies of HOMO and LUMO orbitals, non‐linear optical (NLO) properties (the electronic dipole moment (μ), first‐order hyperpolarizability (β), the hyper‐Rayleigh scattering (β_HRS) and the depolarization ratio (DR)), and other global properties; these calculations showed lower values of β and DR, higher value of β_HRS, and the shortest lengths of the four N?H bonds between TUD1 and salicylate which confirm their strong complexation and salicylate‐selectivity. Also, all the studied anion‐TUD1 exhibited relatively high NLO properties, and these results were considered as a preliminary study for investigating new types of NLO bearing materials. The sensors were applied successfully for the determination of salicylate anion in Aspocid® and Aspirin®.     

Graft copolymerization of hydroxyethyl cellulose with solketal acrylate: Preparation and characterization for moisture absorption application

In this work, we reported the preparation of a novel biomaterial, by graft-polymerization of 2-2-dimethyl-1-3-dioxolan-4-yl methyl acrylate (solketalacrylate, DMDMA) on hydroxyethyl cellulose (HEC) using KPS as initiator. Several experiments were performed to found the optimum conditions for the preparation of this biopolymer, by varying the time of the reaction as well as the initiator and the monomer ratio. Results showed that the highest grafting yield was 25%, obtained after 72?minutes at 65?°C, using THF as solvent. The structure of the grafted copolymer was confirmed by X-ray diffraction patterns which showed, besides the characteristic peaks of HEC at 2θ?=?31.74° and 44.63° a new peak at 2θ?=?30.72° related to an organized structure of the grafted polymer on the HEC backbone. The DSC analysis showed a single glass transition temperature Tg, intermediate between the corresponding values for HEC and neat poly(solketal acrylate). Moreover, the grafted biomaterial presented two-fold more moisture absorption ability by comparison with HEC, making this new synthetic biomaterial highly promising for dryness applications. In our knowledge, the synthesized monomer: 2-2-dimethyl-1-3-dioxolan-4-yl methyl acrylate, (solketal acrylate, DMDMA), has never been grafted on the HEC backbones before that is what makes the novelty of the present work.     

Polymeric membranes based on cellulose acetate loaded with candle soot nanoparticles for water desalination

This study is concerned with modifying cellulose acetate (CA)/polyethylene glycol (PEG) membranes prepared via phase inversion technique in the presence of carbon nanoparticles; candle soot (CS) resulting from combusted candle. CS nanoparticles were analyzed via Fourier transform infrared spectroscopy and transmission electron microscopy. The developed membranes were characterized for their surface morphology, mechanical properties as well as thermal stability. CS nanoparticles contributed in improving the salt rejection % with a slight reduction in the water flux behavior. Employing the annealed cellulose acetate/polyethylene glycol membranes loaded with candle soot nanoparticles provides an adequate approach towards water desalination implementations.     

Manufacturing of pH sensitive PVA/PVP/MWCNT and PVA/PEG/MWCNT nanocomposites: an approach for significant drug release

The purpose of this paper is studying the effect of incorporation of Multiwall Carbon Nanotubes (MWCNT) into two different nanocomposites in poly vinyl alcohol (PVA)/polyvinylpyrrolidone (PVP), and PVA/Polyethylene glycol (PEG). MWCNT were synthesized by chemical vapor deposition (CVD) method using acetylene and Fe/Co/Al₂O₃ as carbon precursor and catalyst, respectively. Nitric acid and sulfuric acid were used for purification and functionalization of MWCNT. Afterward, highly pure and functionalized MWCNT (0, 0.02, and 0.05% w/w) were incorporated in PVA/PVP and PVA/PEG to synthesize PVA/PVP/MWCNT and PVA/PEG/MWCNT nanocomposites hydrogel membranes that cross-linked by freezing–thawing. PEG and PVP were selected in these nanocomposites as dispersion matrix for MWCNT as well as for increasing the elasticity of the nanocomposites membranes. The morphology of the hydrogels was characterized by SEM, FTIR, XRD, TGA, and the mechanical properties of the hydrogel membranes were investigated. The swelling behavior in different pH-buffer solutions was studied as well as studying weight loss percentage and swelling kinetic. The drug releasing process of the hydrogel membranes was investigated using salicylic acid as a model drug. It was found that MWCNT are dispersed well into the polymers and crystallinity, mechanical properties and thermal stability of the hydrogels contain MWCNT are better than that without MWCNT. Maximum degree of swelling was observed at pH 7 and swelling degree increases with increasing the ratio of MWCNT in the hydrogels from 0.02 to 0.05%. All hydrogel membranes followed non-Fickian mechanism and drug releasing were controlled by varying the pH and amount of MWCNT.     

New pyranosyl cembranoid diterpenes from Sarcophyton trocheliophorum

During our continual searching programme for novel bioactive metabolites from Sarcophyton trocheliophorum, collected from Red Sea, we describe herein the isolation and structural elucidation of further two new pyrane-based cembranoid diterpenes: 9-hydroxy-7,8-dehydro-sarcotrocheliol (1) and 8,9-expoy-sarcotrocheliol acetate (2), along with the well-known sarcotrocheliol acetate (3), (+)-sarcophine (4), (+)-sarcophytoxide (5) and (-)-sarcophytoxide (6). The chemical structures of compounds 1 and 2 were determined on the basis of 1D and 2D NMR (¹H, ¹³C, ¹H–¹H COSY, HMQC, HMBC and NOE), mass spectra (ESI and HR-ESIMS) and by comparison with related structures. The antimicrobial activities of the reported compounds 1–6 were investigated. According to the molecular docking study of compounds 1–6 using 3D structure of α,β tubulin in complex with taxol (PDB code 1JFF) and epothilone A (PDB code 1TVK), sarcophine (4) displayed the highest affinity towards both crystal structures, followed by 5 and 6, meanwhile pyrane-based cembranoid diterpenes (1–3) showed less affinity.     

A new flavonol glycoside and other flavonoids from the aerial parts of Taverniera aegyptiaca

Isolation of flavonoids from the aerial parts of Taverniera aegyptiaca Bioss. (Fabaceae) led to identification of one new flavonol glycoside, isorhamnetin-3-O-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside (1), along with eleven compounds, which previously have not been isolated from this plant quercetin-3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)-β-d-galactopyranoside] (2), isorhamnetin-3-O-α-l-arabinopyranoside (3), quercetin-3-O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside (4), isorhamnetin-3-O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside (7), isorhamnetin 3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)-β-d-galactopyranoside] (8), isorhamnetin 3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside] (9), kaempferol 3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)-β-d-galactopyranoside] (10), isorhamnetin (11), 4,4′-dihydroxy-2′-methoxychalcone (12), formononetin (13) and calycosin (15)] and some compounds already known from this plant [quercetin-3-O-robinobioside (5), isorhamnetin-3-O-robinobioside (6), afrormosin (14) and odoratin (16)].     

Polyphenolic profiling of Ipomoea carnea Jacq. by HPLC-DAD and its implications in oxidative stress and cancer

Ipomoea carnea Jacq. is an important folklore medicinal plant, assessed for its underexplored biological potential. Antioxidant, cytotoxic, antiproliferative and polyphenolic profile of whole plant was evaluated using various techniques. Maximum extract recovery (29% w/w), phenolic [13.54 ± 0.27 μg GAE/mg dry weight (DW)] and flavonoid (2.11 ± 0.10 μg QE /mg DW) content were recorded in methanol-distilled water (1:1) flower extract. HPLC-DAD analysis quantified substantial amount of six different polyphenols ranging from 0.081 to 37.95 μg/mg extract. Maximum total antioxidant and reducing potential were documented in methanol-distilled water and acetone-distilled water flower extracts (42.62 ± 0.47 and 24.38 ± 0.39 μg AAE/mg DW) respectively. Ethanol-chloroform root extract manifested highest free radical scavenging (IC₅₀ of 61.22 μg/mL) while 94.64% of the extracts showed cytotoxicity against brine shrimps. Ethanol leaf extract exhibited remarkable activity against THP-1 cell line (IC₅₀ = 8 ± 0.05 μg/mL) and protein kinases (31 mm phenotype bald zone).