Design, Synthesis and Evaluation of Benzimidazole Derivatives as IL-6 Inhibitors and Their Role in Rheumatoid Arthritis.

Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a major role in the development of Rheumatoid Arthritis (RA). In the present study, benzimidazole and benzene sulfonyl scaffold were identified as pharmacophore by analysis of literature reports and novel small molecule IL-6 inhibitors were designed. These were screened via docking with IL-6 (PDB: 1ALU), then and through Lipinski's rule of 5.

A critical analysis of design, binding pattern and SAR of benzo-fused heteronuclear compounds as VEGFR-2 inhibitors.

Vascular endothelial growth factors (VEGFs) are a class of homodimeric ligands that bind to their receptors (VEGFRs) to carryout physiological and pathological angiogenesis essential for regulating homeostasis of body. Overexpression of VEGF results in metastasis of benign tumor into malignant tumor. An active role of VEGFR-2 in cancer angiogenesis makes it a major target for cancer therapy.

Nanoparticle-Shielded dsRNA Delivery for Enhancing RNAi Efficiency in Cotton Spotted Bollworm (Lepidoptera: Nolidae).

The spotted bollworm (Lepidoptera: Nolidae) is a polyphagous pest with enormous economic significance, primarily affecting cotton and okra. However, the lack of gene sequence information on this pest has a significant constraint on molecular investigations and the formulation of superior pest management strategies. An RNA-seq-based transcriptome study was conducted to alleviate such limitations, and de novo assembly was performed to obtain transcript sequences of this pest.

Design, Synthesis and Evaluation of Benzimidazole Hybrids to Inhibit Acetylcholinesterase and COX for Treatment of Alzheimer's Disease.

Background: A simultaneous administration of an acetylcholinesterase (AChE) inhibitor and a NSAID as a drug cocktail has been documented to exhibit significantly protective effects in AD patients. But it suffers from poor patent compliance, pharmacodynamics and pharmacokinetic issues.

Objective: The present study is aimed to design and synthesize a hybrid molecule capable of exhibiting both AChE inhibition and anti-inflammatory activities for de-accelerating the progression of AD.

Prevalence of reproductive drugs usage in humans and animals: A pilot study in Patiala city of India.

Reproductive drugs that include contraceptive and fertility drugs are used to manage reproductive health in both humans and animals. Contraceptive drugs are mainly used by humans for reversible contraception whereas fertility drugs are mainly used in animals to increase milk production, poultry products and meat production. Usage of these drugs has increased manifold in the last decade.

A panoramic review of IL-6: Structure, pathophysiological roles and inhibitors.

Interleukin-6 (IL-6) is a pleiotropic pro-inflammatory cytokine. Its deregulation is associated with chronic inflammation, and multifactorial auto-immune disorders. It mediates its biological roles through a hexameric complex composed of IL-6 itself, its receptor IL-6R, and glycoprotein 130 (IL-6/IL-6R/gp130).

WHO prescribed shelf life assessment of Syzygium cumini extract through chromatographic and biological activity analyses.

Background: Regulatory guidelines recommend shelf life of herbal products to be established through systematic stability studies.

Objective: The study was designed to establish shelf life of Syzygium cumini extract through accelerated and long-term stability testing as per WHO guidelines.

Material And Methods: The extract was stored under accelerated (40°C/75 %RH) and long-term (25°C/60 %RH) stability conditions for 6 and 30 months, respectively.

Assessment of shelf-life of extract through WHO recommended stability study involving chromatographic and biological activity analyses.

Stability study on extract under WHO recommended accelerated and long-term conditions for 6 and 30 months, respectively was carried out by taking gymnemagenin as a marker and by evaluating antidiabetic activity through different models. Gymnemagenin was not detected in any stability sample indicating that gymnemic acids (GAs) remain stable in the extract under the test conditions. The extract and its GA rich fraction exhibited mild α-glucosidase inhibitory activity (18-27%) that remained same during the study.

Inducible nitric oxide synthase inhibitors: A comprehensive update.

Inducible nitric oxide synthase (iNOS), which is expressed in response to bacterial/proinflammatory stimuli, generates nitric oxide (NO) that provides cytoprotection. Overexpression of iNOS increases the levels of NO, and this increased NO level is implicated in pathophysiology of complex multifactorial diseases like Parkinson's disease, Alzheimer's disease, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Selective inhibition of iNOS is an effective approach in treatment of such complex diseases.

Novel Coupled Molecules from Active Structural Motifs of Synthetic and Natural Origin as Immunosuppressants.

Introduction: Nitric oxide (NO) is an important mediator in the pathogenesis and control of immune system-related disorders and its levels are modulated by inducible NO synthase (iNOS). Oxidative stress is another pathological indication in majority of autoimmune disorders. The present study aims at the development of coupled molecules via selection of pharmacophores for both immunomodulatory and antioxidant activities through iNOS inhibition.

Reproductive drugs and environmental contamination: quantum, impact assessment and control strategies.

Industrial and municipal solid wastes, noise, pesticides, fertilizers and vehicular emission are visible pollutants responsible for environmental contamination and ill-effects on health of all living systems. But, environmental contamination due to drugs or medicines used for different purposes in humans and animals goes unseen largely and can affect the health of living system severely. During the last few decades, the usage of drugs has increased drastically, resulting in increased drug load in soil and water.

Antimicrobial Potential of Benzimidazole Derived Molecules.

Structural resemblance of benzimidazole nucleus with purine nucleus in nucleotides makes benzimidazole derivatives attractive ligands to interact with biopolymers of a living system. The most prominent benzimidazole compound in nature is N-ribosyldimethylbenzimidazole, which serves as an axial ligand for cobalt in vitamin B12. This structural similarity prompted medicinal chemists across the globe to synthesize a variety of benzimidazole derivatives and to screen those for various biological activities, such as anticancer, hormone antagonist, antiviral, anti-HIV, anthelmintic, antiprotozoal, antimicrobial, antihypertensive, anti-inflammatory, analgesic, anxiolytic, antiallergic, coagulant, anticoagulant, antioxidant and antidiabetic activities.

Bioanalytical Method Validation for Dronedarone and Duloxetine in Blood Serum.

The present work relates to the development and validation of reversed-phase HPLC-UV-photodiode array methods for the estimation of two drugs in blood serum: dronedarone hydrochloride (DDN), a class III antiarrhythmic drug, and duloxetine hydrochloride (DLX), an antidepressant. Chromatographic analysis of DLX was carried out on a Nucleodur C18 column (250 × 4.6 mm, 5 μm) using ammonium acetate buffer (32 mM, pH 5.

Accelerated Stability Studies on Dried Extracts of Centella asiatica Through Chemical, HPLC, HPTLC, and Biological Activity Analyses.

Regulatory guidelines recommend systematic stability studies on a herbal product to establish its shelf life. In the present study, commercial extracts (Types I and II) and freshly prepared extract (Type III) of Centella asiatica were subjected to accelerated stability testing for 6 months. Control and stability samples were evaluated for organoleptics, pH, moisture, total phenolic content (TPC), asiatic acid, kaempherol, and high-performance thin layer chromatography fingerprints, and for antioxidant and acetylcholinesterase inhibitory activities.

Stability Testing of Herbal Drugs: Challenges, Regulatory Compliance and Perspectives.

Stability testing is an important component of herbal drugs and products (HDPs) development process. Drugs regulatory agencies across the globe have recommended guidelines for the conduct of stability studies on HDPs, which require that stability data should be included in the product registration dossier. From the scientific viewpoint, numerous chemical constituents in an herbal drug are liable to varied chemical reactions under the influence of different conditions during its shelf life.

Characterization of stress degradation products of duloxetine hydrochloride employing LC-UV/PDA and LC-MS/TOF studies.

Duloxetine HCl was subjected to forced degradation under conditions of hydrolysis (neutral, acidic and alkaline), oxidation, photolysis and thermal stress, as suggested in the ICH guideline Q1A(R2). The drug showed significant degradation under acidic, alkaline and aqueous hydrolytic as well as photolytic conditions. The drug remained stable under thermal and oxidative stress conditions.

Forced degradation, LC-UV, MS(n) and LC-MS-TOF studies on azilsartan: Identification of a known and three new degradation impurities.

In the present study, Azilsartan (AZL) was subjected to ICH recommended forced degradation conditions of hydrolysis, oxidation, dry heat and photolysis. The drug degraded to four degradation products (I-IV) under acidic, alkaline and water hydrolysis and photolysis. All the four degradation products were resolved in a single run on a C-18 column (250mm×4.

Novel coumarin-benzimidazole derivatives as antioxidants and safer anti-inflammatory agents.

Inspired from occurrence of anti-inflammatory activity of 3-substituted coumarins and antiulcer activity of various 2-substituted benzimidazoles, novel compounds have been designed by coupling coumarin derivatives at 3-position directly or through amide linkage with benzimidazole nucleus at 2-position. The resultant compounds are expected to exhibit both anti-inflammatory and antioxidant activities along with less gastric toxicity profile. Two series of coumarin-benzimidazole derivatives (4a-e and 5a-e) were synthesized and evaluated for anti-inflammatory activity and antioxidant activity.

Identification and characterization of stress degradation products of dronedarone hydrochloride employing LC-UV/PDA, LC-MS/TOF and MS(n) studies.

Dronedarone HCl was subjected to forced decomposition conditions of hydrolysis (neutral, acidic and alkaline), oxidation, photolysis and thermal stress, as suggested in the ICH guideline Q1A(R2). The drug showed significant degradation under alkaline hydrolytic and alkaline photolytic conditions while it remained stable in neutral, acidic, thermal and oxidative conditions. In total, six degradation products (I-VI) were formed, which could be separated by chromatography on C18 (250 mm × 4.

Four new degradation products of doxorubicin: An application of forced degradation study and hyphenated chromatographic techniques.

Forced degradation study on doxorubicin (DOX) was carried out under hydrolytic condition in acidic, alkaline and neutral media at varied temperatures, as well as under peroxide, thermal and photolytic conditions in accordance with International Conference on Harmonization (ICH) guidelines Q1(R2). It was found extremely unstable to alkaline hydrolysis even at room temperature, unstable to acid hydrolysis at 80 °C, and to oxidation at room temperature. It degraded to four products (O-I-O-IV) in oxidative condition, and to single product (A-I) in acid hydrolytic condition.

Identification of four new degradation products of epirubicin through forced degradation, LC-UV, MSn and LC-MS-TOF studies.

Epirubicin (EPI) was subjected to International Conference on Harmonization recommended forced degradation under the conditions of hydrolysis, oxidation, dry heat and photolysis to characterize its possible impurities and/or degradation products. The drug was found highly unstable to alkaline hydrolysis even at room temperature, unstable to acid hydrolysis at 80°C and to oxidation at room temperature. The hydrolytic and oxidative degradation products were resolved on an Agilent RP8 (150 mm × 4.

Isolation and characterization of a degradation product in leflunomide and a validated selective stability-indicating HPLC-UV method for their quantification.

Leflunomide (LLM) is subjected to forced degradation under conditions of hydrolysis, oxidation, dry heat, and photolysis as recommended by International Conference on Harmonization guideline Q1A(R2). In total, four degradation products (I-IV) were formed under different conditions. Products I, II and IV were formed in alkaline hydrolytic, acidic hydrolytic and alkaline photolytic conditions.

Coumarin: a promising scaffold for anticancer agents.

Coumarin enjoys an important place in drug discovery process due to its presence in diversity of biologically active compounds. Many compounds of plant origin are derivatives of coumarin. Taking these natural products as lead, research groups across the globe have designed and synthesized numerous coumarin analogues for treatment of varied diseases.

Degradation Study on Sulfasalazine and a Validated HPLC-UV Method for its Stability Testing.

Sulfasalazine (SSZ) was subjected to degradation under the conditions of hydrolysis (acid, alkali, and water), oxidation (30% H2O2), dry heat, and photolysis (UV-VIS light) in accordance with the ICH guidelines. An RP-HPLC method was developed to study the degradation behavior. No degradation was noted under any condition except alkaline hydrolysis where SSZ was degraded to a single minor product.