Exploring antibiofilm potential of some new imidazole analogs against synthesis, antifungal activity, molecular docking and molecular dynamics studies.

A series of 1, 2, 4, 5-tetrasubstituted imidazole derivatives were synthesized and their antibiofilm potential against was evaluated . Two of the synthesized derivatives IC= 25 µg/mL) and (IC= 6 µg/mL),displayed better antifungal and antibiofilm potential than the standard drug Fluconazole (IC = 40 µg/mL) against . Based on the results, we escalated the real time polymerase chain reaction (RT-PCR) analysis to gain knowledge of the enzymes expressed in the generation and maintenance of biofilms and the mechanism of biofilm inhibition by the synthesized analogues.

Insilico structure based drug design approach to find potential hits in ventilator-associated pneumonia caused by Pseudomonas aeruginosa.

Tetraacyldisaccharide 4'-kinase (LpxK) is the prime enzyme responsible for the biosynthesis of lipid A. LpxK is a key antibacterial drug target, but it is less exploitation in Pseudomonas aeruginosa and other bacterial species limits its therapeutic use. Pseudomonas aeruginosa is responsible for severe infections like pneumonia and urinary tract infections.

Efficient gene transfection to lung cancer cells via Folate-PEI-Sorbitol gene transporter.

Lung cancer is known to be one of the fatal diseases in the world and is experiencing treatment difficulties. Many treatments have been discovered and implemented, but death rate of patients with lung cancer continues to remain high. Current treatments for cancer such as chemotherapy, immunotherapy, and radiotherapy have shown considerable results, yet they are accompanied by side effects.

Development of novel, biocompatible, polyester amines for microglia-targeting gene delivery.

Recent progress in personalized medicine and gene delivery has created exciting opportunities in therapeutics for central nervous system (CNS) disorders. Despite the interest in gene-based therapies, successful delivery of nucleic acids for treatment of CNS disorders faces major challenges. Here we report the facile synthesis of a novel, biodegradable, microglia-targeting polyester amine (PEA) carrier based on hydrophilic triethylene glycol dimethacrylate (TG) and low-molecular weight polyethylenimine (LMW-PEI).

Recent advances in B-RAF inhibitors as anticancer agents.

The significance of B-RAF in the promotion of cell proliferation and motility was explored by the researchers in the past. However, in 2002, several researchers found that mutation in B-RAF leads to cancer. Extensive research on B-RAF mutations suggested B-RAF V600E mutation as a critical predictive, prognostic and diagnostic biomarker in numerous cancers such as melanoma, thyroid, and colorectal cancers.

Insights of tankyrases: A novel target for drug discovery.

Tankyrases are the group of enzymes belonging to a class of Poly (ADP-ribose) polymerase (PARP) recently named ADP-ribosyltransferase (ARTD). The two isoforms of tankyrase i.e.

Molecular docking, pharmacophore based virtual screening and molecular dynamics studies towards the identification of potential leads for the management of .

The enzyme pantothenate synthetase panC is one of the potential new antimicrobial drug targets, but it is poorly characterized in . infection can cause gastric cancer and the management of infection is crucial in various gastric ulcers and gastric cancer. The current study describes the use of innovative drug discovery and design approaches like comparative metabolic pathway analysis (Metacyc), exploration of database of essential genes (DEG), homology modelling, pharmacophore based virtual screening, ADMET studies and molecular dynamics simulations in identifying potential lead compounds for the specific panC.

Synthesis and biological activity of structurally diverse phthalazine derivatives: A systematic review.

Phthalazine, a structurally and pharmacologically versatile nitrogen-containing heterocycle, has gained more attention from medicinal chemists in the design and synthesis of novel drugs owing to its pharmacological potential. In particular, phthalazine scaffold appeared as a pharmacophoric feature numerous drugs exhibiting pharmacological activities, in particular, antidiabetic, anticancer, antihypertensive, antithrombotic, anti-inflammatory, analgesic, antidepressant and antimicrobial activities. This review presents a summary of updated and detailed information on phthalazine as illustrated in both patented and non-patented literature.

Sugar alcohol-based polymeric gene carriers: Synthesis, properties and gene therapy applications.

Advances in the field of nanomedicine have led to the development of various gene carriers with desirable cellular responses. However, unfavorable stability and physicochemical properties have hindered their applications in vivo. Therefore, multifunctional, smart nanocarriers with unique properties to overcome such drawbacks are needed.

Biodegradable Polymeric Nanocarrier-Based Immunotherapy in Hepatitis Vaccination.

Various commercial vaccines are used for immunization against hepatitis B. However, these immunotherapeutic vaccines require invasive administration, which can induce side effects, and require multiple shots to elicit an immune response, limiting their efficacy. Compared to traditional hepatitis B vaccines, polymer nanoparticles have more advantageous inherent properties as vaccine delivery carriers, providing increased stability of encapsulated antigen, the possibility of single-shot immunotherapy, and the capability of mucosal administration, which allows various routes of vaccination.

Targeted Delivery of siRNA Therapeutics using Ligand Mediated Biodegradable Polymeric Nanocarriers.

Background: Cancer poses a major public health issue, is linked with high mortality rates across the world, and shows a strong interplay between genetic and environmental factors. To date, common therapeutics, including chemotherapy, immunotherapy, and radiotherapy, have made significant contributions to cancer treatment, although diverse obstacles for achieving the permanent "magic bullet" cure have remained. Recently, various anticancer therapeutic agents designed to overcome the limitations of these conventional cancer treatments have received considerable attention.

Sugar-based gene delivery systems: Current knowledge and new perspectives.

Carbohydrates, one of the most abundant natural compounds and key participants in many biological processes, are relevant in medical and industrial fields. In comparison with synthetic polymers, carbohydrates are biocompatible and have intrinsic targeting properties, enabling them to interact with cell-surface receptors. Among the different carbohydrates, polysaccharides are naturally occurring biological molecules with tremendous potential for biomedical applications.

Bacterial Peptide Deformylase Inhibition of Tetrazole-Substituted Biaryl Acid Analogs: Synthesis, Biological Evaluations, and Molecular Docking Study.

The synthesis and screening of tetrazole-substituted biaryl acid analogs 7a-l as bacterial peptide deformylase (PDF) enzyme inhibitors is reported. The compounds 7e (IC value = 5.50 μM) and 7g (IC value = 7.

Biphenyl tetrazole-thiazolidinediones as novel bacterial peptide deformylase inhibitors: Synthesis, biological evaluations and molecular docking study.

Herein, we report the synthesis and screening of biphenyl tetrazole-thiazolidinediones 14(a-j) as bacterial Peptide deformylase (PDF) enzyme inhibitors. The compounds 14b (IC value=16.25μM), 14c (IC value=18.

Correction: Efficient gene transfection to liver cells via the cellular regulation of a multifunctional polylactitol-based gene transporter.

Correction for 'Efficient gene transfection to liver cells via the cellular regulation of a multifunctional polylactitol-based gene transporter' by Young-Dong Kim et al., J. Mater.

Gene therapy for bone tissue engineering.

Gene therapy holds a great promise and has been extensively investigated to improve bone formation and regeneration therapies in bone tissue engineering. A variety of osteogenic genes can be delivered by combining different vectors (viral or non-viral), scaffolds and delivery methodologies. gene enhanced tissue engineering approaches have led to successful osteogenic differentiation and bone formation.

Efficient gene transfection to liver cells via the cellular regulation of a multifunctional polylactitol-based gene transporter.

In recent years, the introduction of non-viral gene transfer systems for the treatment of inherited and acquired liver diseases has attracted a lot of attention. To facilitate liver-directed gene delivery, a liver cell targeting strategy and a intracellular control of gene trafficking for the design of an ideal non-viral gene delivery system are crucial and a great challenge. In order to meet these needs, a new multifunctional gene carrier, the polylactitol-based gene transporter (PLT), was prepared by crosslinking low molecular weight polyethylenimine (LMW PEI) with lactitol diacrylate (LDA) composed of d-galactose and d-sorbitol.

Image-Guided Nanoparticle-Based siRNA Delivery for Cancer Therapy.

With the discovery of RNA interference technology, small-interfering RNA (siRNA) has emerged as new powerful tool for gene therapy because of its high targeting specificity and selectivity. However, one of the limitations to successful gene therapy is the inability to monitor delivery of genes and therapeutic responses at the targeted site. Hence, a combinatorial approach of gene therapy with molecular imaging has been crucial in optimizing gene therapy.

Nanoparticle-mediated delivery of siRNA for effective lung cancer therapy.

Lung cancer is one of the most lethal diseases worldwide, and the survival rate is less than 15% even after the treatment. Unfortunately, chemotherapeutic treatments for lung cancer are accompanied by severe side effects, lack of selectivity and multidrug resistance. In order to overcome the limitations of conventional chemotherapy, nanoparticle-mediated RNA interference drugs represent a potential new approach due to selective silencing effect of oncogenes and multidrug resistance related genes.

Aerosol delivery of beclin1 enhanced the anti-tumor effect of radiation in the lungs of K-rasLA1 mice.

Radiotherapy alone has several limitations for treating lung cancer. Inhalation, a non-invasive approach for direct delivery of therapeutic agents to the lung, may help to enhance the therapeutic efficacy of radiation. Up-regulating beclin1, known as a tumor suppressor gene that plays a major role in autophagy, may sensitize tumors and lead to tumor regression in lungs of K-ras(LA1) lung cancer model mice.

Accelerated gene transfer through a polysorbitol-based transporter mechanism.

Here we report an accelerated gene transfer through a polysorbitol-based osmotically active transporter (PSOAT) that shows several surprising results through interesting mechanisms. The nano-sized and well-complexed PSOAT/DNA particles are less toxic, stable at serum and show no aggregation after lyophilization due to their polysorbitol backbone. The transfection is remarkably accelerated both in vitro and in vivo, presumably due to a transporter mechanism of PSOAT in spite of possibility of reduction of transfection by many hydroxyl groups in the transporter.

Mucoadhesive and pH-sensitive thiolated Eudragit microspheres for oral delivery of Pasteurella multocida antigens containing dermonecrotoxin.

In this study, cysteine was conjugated to the Eudragit to have mucoadhesive and pH-sensitive properties. Pasteurella multocida dermonecrotoxin (PMT) is a major virulence factor as a causative agent of atrophic rhinitis (AR) in swine and, therefore, inactivated P. multocida was used as a candidate vaccine in the current study.

Degradable poly(amido amine)s as gene delivery carriers.

Introduction: In recent years, there has been a great deal of interest in the development of vectors which are being developed based on the capacity of polymers to mediate appropriate interactions with the cellular environment, or to interface with specific cellular processes. Several such vectors have been synthesized, resulting in biomacromolecules with low cytotoxicity and higher gene delivery ability.

Areas Covered: This review briefly describes the recent success of poly(amido amine)s (PAAs) as non-viral vectors, and highlights their promising future in the development of nucleic acid-based therapy.

pH-Responsive Polymers as Gene Carriers.

Despite the immense potential of non-viral delivery system in gene therapy its application has been impaired greatly by various impediments having contrasting traits. Therefore it is an absolute necessity to develop some non-viral vectors which are endowed with special characteristics to act differently in intracellular as well as extracellular compartments to surmount these inter-conflicting hurdles. Such smart polymers should serve some specific purposes by adjusting their structural or functional traits under the influence of stimuli such as temperature, light, salt concentration or pH.

Chitosan-graft-spermine as a gene carrier in vitro and in vivo.

Chitosan has been proposed as a non-viral gene carrier because of its biodegradable and biocompatible cationic polymeric properties. However, the transfection efficiency of chitosan-DNA complexes is still too low for clinical trials. To improve transfection efficiency, we prepared a chitosan-graft-spermine (CHI-g-SPE) copolymer by an imine reaction between periodate-oxidized chitosan and spermine.