Self-Assembled Nanoparticles Based on Block-Copolymers of Poly(2-deoxy-2-methacrylamido-d-glucose)/Poly(N-vinyl succinamic acid) with Poly(O-cholesteryl methacrylate) for Delivery of Hydrophobic Drugs

The self-assembly of amphiphilic block-copolymers is a convenient way to obtain soft nanomaterials of different morphology and scale. In turn, the use of a biomimetic approach makes it possible to synthesize polymers with fragments similar to natural macromolecules but more resistant to biodegradation. In this study, we synthesized the novel bio-inspired amphiphilic block-copolymers consisting of poly(N-methacrylamido-d-glucose) or poly(N-vinyl succinamic acid) as a hydrophilic fragment and poly(O-cholesteryl methacrylate) as a hydrophobic fragment. Block-copolymers were synthesized by radical addition–fragmentation chain-transfer (RAFT) polymerization using dithiobenzoate or trithiocarbonate chain-transfer agent depending on the first monomer, further forming the hydrophilic block. Both homopolymers and copolymers were characterized by 1H NMR and Fourier transform infrared spectroscopy, as well as thermogravimetric analysis. The obtained copolymers had low dispersity (1.05–1.37) and molecular weights in the range of ~13,000–32,000. The amphiphilic copolymers demonstrated enhanced thermal stability in comparison with hydrophilic precursors. According to dynamic light scattering and nanoparticle tracking analysis, the obtained amphiphilic copolymers were able to self-assemble in aqueous media into nanoparticles with a hydrodynamic diameter of approximately 200 nm. An investigation of nanoparticles by transmission electron microscopy revealed their spherical shape. The obtained nanoparticles did not demonstrate cytotoxicity against human embryonic kidney (HEK293) and bronchial epithelial (BEAS-2B) cells, and they were characterized by a low uptake by macrophages in vitro. Paclitaxel loaded into the developed polymer nanoparticles retained biological activity against lung adenocarcinoma epithelial cells (A549).

Crystal Structure, Hirshfeld Surface and Frontier Molecular Orbital Analyses of N-[2-(trifluoromethyl)phenyl]succinamic Acid

The ortho-CF3 substituent and the N-H bond are in syn-conformation in N-[2-(trifluoromethyl)phenyl]succinamic acid. In amide and acid functionalities, the carbonyl groups are directed in opposite directions to each other and their related-CH2 groups. syn-Conformation is observed for the acid functionality, where the carbonyl C=O and hydroxyl O-H bonds are directed in the same direction. Three planar fragments comprise of the molecule: aromatic ring (A), core portion -Carm-N(H)-C(=O)-C(H2)-C(H2)(B) and -C(H2)-C(=O)-OH(C). The dihedral angle between a pair of fragments being 48.6(4)º (A and B), 81.6 (4)º (B and C) and 70.5 (5)º (A and C). N-H•••O hydrogen bonds bind the molecules forming C(4) chains in the crystal, and the neighbouring anti-parallel chains are bound by O-H•••O hydrogen bonds resulting in a chair shaped ribbon of one-dimensional nature. The Hirshfeld surface study was carried out, including fingerprint plots. Studies have shown that the interactions with O•••H/H•••O (27.4%), H•••H (27.3%) and H•••F/F•••H (20.2%) substantially added to the surface. Theoretically, the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO) and various global reactivity descriptors were also computed by the density functional theory (DFT/B3LYP) approach with a 6-311G(d, p) basis set in the ground state on the geometrically optimized structure in the gas phase.

Effect of a novel succinamic acid derivative as potential anti-diabetic agent in experimental diabetic rats

4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid which is a succinamic acid derivative has been synthesized in 3 step reaction with malic acid. Its structure confirmation was done by various techniques like 1H NMR, 13C NMR, & HRMS and is recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study, the effect of 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid on plasma glucose, serum insulin, serum lipid profile and lipid peroxidation in streptozotocin–nicotinamide induced type 2 diabetic model was investigated. 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid was administered orally (20 mg/kg b.w.) to streptozotocin + nicotinamide (STZ + NAD) induced diabetic rats for 28 days. A significant increase in fasting blood glucose levels, HbA1c levels, Serum lipid profile (TG & TC) and in the levels of Malonaldialdehyde (MDA, end product of lipid peroxidation) was observed in STZ +NAD diabetic rats whereas the levels of high density lipoprotein-cholesterol (HDL-C) and serum insulin levels were significantly decreased in STZ + NAD induced diabetic rats The effect of 4-((benzyloxy)amino)-2-hydroxy-4-oxobutanoic acid was compared with glibenclamide, a reference drug. Treatment with 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid and glibenclamide resulted in a significant reduction of fasting blood glucose levels with increase in plasma insulin levels in diabetic treated rats. 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid also resulted in a significant improvement in serum lipids and lipid peroxidation products. Our results suggest the potential role of 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid in the management of type-2 diabetes mellitus experimental rats. Keywords: 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid, dyslipidemia, streptozotocin induced diabetes, lipid peroxidation

Karakterisasi Morfologi dan Pemanfaatan Sumber Karbon oleh Khamir Antagonis Patogen Antraknosa

Karakterisasi morfologi khamir penting dilakukan sebagai pengenalan awal suatu isolat khamir. Sedangkan, pengamatan terhadap pemanfaatan sumber karbon digunakan untuk mengetahui sumber karbon yang dapat digunakankan oleh khamir untuk perbanyakan dan peningkatan kemampuannya sebagai agens biokontrol. Penelitian ini bertujuan untuk mengkarakterisasi morfologi dan mengetahui pemanfaatan sumber karbon oleh khamir antagonis patogen antraknosa pada cabai (Colletotrichum acutatum). Karakterisasi morfologi khamir dilakukan dengan mengamati secara makroskopis koloni enam spesies khamir dalam medium PDA. Karakterisasi morfologi juga dilakukan dengan mengamati mikroskopis sel khamir di bawah mikroskop cahaya photomicrograph multi eyepiece (Zeiss Axiocam). Pengamatan pemanfaatan sumber karbon oleh khamir dilakukan dengan menggunakan BIOLOGTM (MicrologTM System, Release 5.2). Karakteristik morfologi enam spesies khamir antagonis menunjukkan bahwa koloni khamir didominasi warna krem keputihan dengan permukaan kasar, kusam, dan tepi koloni tidak rata. Karakteristik sel secara mikroskopis menunjukkan bentuk sel didominasi oleh bentuk silinder, dengan ukuran bervariasi. Sebagian besar khamir bersifat dimorfik. Pengamatan pemanfaatan sumber karbon oleh khamir antagonis menunjukkan Aureobasidium pullulans, Pseudozyma hubeiensis, Pseudozyma aphidis dan Pseudozyma shanxiensis dapat memanfaatkan 20 sumber karbon yang sama yaitu Tween 80, Arbutin, D-Gluconic Acid, D-Glucuronic Acid, D-Ribose, Salicin, ɤ-AminoButyric Acid, Bromosuccinic Acid, Fumaric Acid, β-Hydroxy Butyric Acid, L-Lactic Acid, LMalic Acid, Succinamic Acid, Succinic Acid, Alaninamide, L-Alanine, L-Aspartic Acid, LGlutamic Acid, Putrecine, dan Quinic Acid. Sedangkan, dua spesies khamir yaitu Rhodotorula minuta dan Candida tropicalis dapat memanfaatkan dua sumber karbon yang sama yaitu D-Trehalose dan D-Galactose plus D-Xylose.

In-MOFs based on amide functionalised flexible linkers

Two new amide functionalised metal–organic frameworks, In(OH)CSA and In(OH)PDG, were synthesized using two flexible linkers, N-(4-carboxyphenyl)succinamic acid (CSA) and N,N′-(1,4-phenylenedicarbonyl)diglycine (PDG), respectively. Both structures consist of corner-sharing {InO4(OH)2} octahedra in the form of trans indium hydroxide chains, which are interconnected by the dicarboxylate linkers to form stacked 2-dimensional layers. The different symmetries and configurations of the flexible and rigid features on the linkers results in different supramolecular interactions dominating between linkers, resulting in different shaped pores and functional group orientation. In(OH)CSA lacks hydrogen bonding between linkers, which results in close packing between the layers and very small solvent accessible pores running perpendicular to the plane of the layers. In(OH)PDG exhibits strong intra- and interlayer hydrogen bonding, which prevents the layers from close packing and results in larger cylindrical pores running parallel to the indium hydroxide chains, producing a total accessible volume of 25% of the unit cell volume.