Alectinib Synthesis through Formal α-Arylation of Enone.

A new synthetic route for the synthesis of Alectinib, which is used as an adjuvant and first line of treatment in ALK-positive non-small cell lung cancer, is reported. The developed route starts from readily available starting materials (4-(4-methoxyphenyl)butyric acid or 2-ethyl anisole) and employs Suzuki-Miyaura cross-coupling and reductive cyclization as key steps. Good yield and no regioisomeric mixture formation are the key highlights of this route.

Photocatalytic oxidative hydroacylation with alcohols.

Herein, we report a photocatalytic method for oxidative hydroacylation with alcohols. Under photoirradiation and a catalytic amount of TBADT, different electrophiles (azodicarboxylates, -phenylmaleimide, benzylidenemalononitrile and phenyl vinyl sulfone) underwent hydroacylation with alcohols in good yields. The method was also applied to achieve a convenient synthesis of the anti-depressant drug moclobemide.

Photoinduced [4+2] cycloaddition of dienes and quinonemethides.

A visible light-induced cycloaddition of 1,3-dienes and -quinonemethides through EDA complexation is reported. The reaction does not require any external photocatalyst, oxidant or additive. The generality of the method is established through a broad substrate scope.

Organocatalyzed Hydroacylation of Enones by Photosensitization of Acyl Silanes.

A mild protocol for hydroacylation of enones through photosensitization of acyl silanes with thioxanthone under blue light (455 nm) irradiation is reported. A Brønsted acid is used as a cocatalyst in the reaction. The versatility of the method is demonstrated through inter- and intramolecular hydroacylation reaction.

Organocatalytic photoinduced carboamination of dienes.

An organocatalytic photoinduced 1,2-carbofunctionalization strategy for conjugated dienes has been developed. No exogenous photocatalyst or additives are required in this mild protocol and it allows for highly regioselective and efficient 1,2-carboisothiocyanation through the coupling of a diene, an alkyl radical and TMSNCS. The reaction is proposed to proceed through EDA complexation between the diene and TMSNCS.

Phase III, Randomized, Double-blind, Placebo controlled trial of Efficacy, Safety and Tolerability of Antiviral drug Umifenovir vs Standard care of therapy in non-severe COVID-19 patients.

Objective: To test efficacy, safety and tolerability of Umifenovir in non-severe COVID-19 adult patients.

Methods: We carried out randomized, double-blind, placebo-controlled, multicenter, phase III trials involving adult (18-75 years), non-severe COVID19 patients, randomized 1:1 on placebo or Umifenovir (800 mg BID, maximum 14 days) respectively along with standard-of-care. The primary endpoint for Asymptotic-mild patients was time to nasopharyngeal swab RT-PCR test negativity.

Evidence-Based Discriminant Analysis: A New Insight into Iron Profile for the Diagnosis of Parkinson's Disease.

Introduction: Parkinson's disease is the second most common neurodegenerative disorder. Neurochemical studies have implicated metals in pathogenesis of PD.

Objectives: To examine the association of serum iron, transferrin, ferritin, transferrin saturation and UIBC in PD patients and to derive the Discrimination Function with scores of these variables to correctly classify PD cases and healthy controls.

Survival Analysis: Where, Why, What and How?

Durations of any event, such as duration of hospitalization, is usually found to have a highly skewed distribution and incomplete values due to dropouts and limited follow-up. The usual methods of statistical analysis are, therefore, not applicable. The method of survival analysis is a nonparametric method and is designed to overcome these problems.

Brønsted acid catalyzed radical addition to quinone methides.

A fundamental quest for alkyl radical generation under mild conditions through photoinduced Brønsted acid catalysis is addressed. The optimized protocol does not require any organic dyes or transition metal photocatalyst. Under blue light irradiation with diphenyl phosphate as a catalyst and dihydropyridine derivatives as a radical source, functionalized arylmethane derivatives are obtained in high yield.

Catalytic Enantioselective Synthesis of Aryl-Methyl Organophosphorus Compounds.

A catalytic enantioselective protocol for the synthesis of aryl-methyl organophosphorus compounds is reported. Utilizing a chiral phosphoric acid as a catalyst, a wide range of indole derivatives reacted with phosphorylated quinomethanes in high yield with excellent enantioselectivity. This is the first report on the application of phosphorylated quinomethanes in asymmetric synthesis.

Correction to: a facile approach for fabricating CD44-targeted delivery of hyaluronic acid-functionalized PCL nanoparticles in urethane-induced lung cancer: Bcl-2, MMP-9, caspase-9, and BAX as potential markers.

In the original article the blots for BAX were inadvertently flipped in Fig. 11a. The inadvertent error in the case of BAX does not change any of the results.

Lewis Base/Brønsted Acid Cocatalysis for Thiocyanation of Amides and Thioamides.

Lewis base/Brønsted acid cocatalysis for electrophilic thiocyanation of olefins is reported. Using a combination of triphenylphosphine selenide and diphenyl phosphate as a catalyst, a wide range of unsaturated amides and thioamides underwent thiocyanation to furnish thiocyanated thiazoline and oxazoline derivatives in high yields (up to 97%).

A synergistic approach for management of lung carcinoma through folic acid functionalized co-therapy of capsaicin and gefitinib nanoparticles: Enhanced apoptosis and metalloproteinase-9 down-regulation.

Background: Lung cancer is one of the most lethal cancers and lacks effective treatment strategy. Therapeutic efficacy can be improved through active targeting approach utilizing surface engineered nanoparticles (NPs) for cancer therapy.

Purpose: The present study envisioned development of Folic acid (FA) functionalized NPs for co-administration of gefitinib (Gnb) and capsaicin (Cap) respectively to enhance the therapeutic outcome by disabling the barriers related to tumors extracellular matrix.

Biotinylated naringenin intensified anticancer effect of gefitinib in urethane-induced lung cancer in rats: favourable modulation of apoptotic regulators and serum metabolomics.

Co-therapy through biotin modified nanoparticles (NPs) of gefitinib (Gnb) and naringenin (Nar) was investigated for its therapeutic and synergistic potential against lung cancer. The biotin-conjugated polymeric NPs (bty-Nar/Gnb) were developed using oil in water emulsion technique and optimized using central composite design. The formulations were subjected to various in vitro (A549 cell lines) and in vivo evaluations in urethane-induced lung cancer.

A facile approach for fabricating CD44-targeted delivery of hyaluronic acid-functionalized PCL nanoparticles in urethane-induced lung cancer: Bcl-2, MMP-9, caspase-9, and BAX as potential markers.

Lung carcinoma ranks highest in cancer-related death (about 20% of total cancer deaths) due to poor prognosis and lack of efficient management therapy. Owing to the lack of effective therapeutic approaches, survival rate of less than 5 years persists over the years among non-small cell lung cancer (NSCLC) patients. Capsaicin (CAP) is well reported for its antiproliferative and antioxidant properties in various literature but lacks an appropriate delivery carrier.

QbD-based development of α-linolenic acid potentiated nanoemulsion for targeted delivery of doxorubicin in DMBA-induced mammary gland carcinoma: in vitro and in vivo evaluation.

Breast cancer is the most common cancer of occurrence in women and has the highest mortality incidence rate therein. The present study envisaged to develop doxorubicin (Dox) loaded folate functionalized nanoemulsion (NE) for profound therapeutic activity against mammary gland cancer. NE was prepared using pseudo-ternary phase diagrams utilizing α-linolenic acid (ALA) as lipid phase, to further enhance the anticancer potential of Dox.

ω-3 Fatty Acid Synergized Novel Nanoemulsifying System for Rosuvastatin Delivery: In Vitro and In Vivo Evaluation.

The present study was undertaken to improve rosuvastatin (RSV) bioavailability and pharmacological response through formation of SNES using Perilla frutescens oil as lipid carrier. The composition of oil was estimated by fatty acid methyl ester (FAME) analysis using gas chromatography. Solubility of RSV in Perilla frutescens oil and Cremophor EL was 25.

Photoredox ketone catalysis for the direct C-H imidation and acyloxylation of arenes.

The photoexcited aryl ketone-catalyzed C-H imidation of arenes and heteroarenes is reported. Using 3,6-dimethoxy-9-thioxanthen-9-one as a catalyst in combination with a bench-stable imidating reagent, C-N bond formation proceeds with high efficiency and a broad substrate scope. A key part of this method is that the thioxanthone catalyst acts as an excited-state reductant, thus establishing an oxidative quenching cycle for radical aromatic substitution.

Colloidal Vesicular System of Inositol Hexaphosphate to Counteract DMBA Induced Dysregulation of Markers Pertaining to Cellular Proliferation/Differentiation and Inflammation of Epidermal Layer in Mouse Model.

Cancer is a global health problem and chemoprevention is a promising approach for reducing cancer burden. Inositol hexaphosphate (IP6), a natural bioactive constituent of cereals, legumes, etc., has momentous potential as an antiangiogenic agent, that specifically affects malignant cells.

Oral delivery of allopurinol niosomes in treatment of gout in animal model.

Context: Gout is a painful disorder which does not have an efficient delivery system for its treatment.

Objective: Development and in vitro, in vivo evaluation of allopurinol-loaded nonionic surfactant-based niosomes was envisaged.

Materials And Methods: Niosomes were prepared with Span 20 and Tween 20 (1:1 molar ratio) using ether injection method.

Systematic development of optimized SNEDDS of artemether with improved biopharmaceutical and antimalarial potential.

The current studies entail systematic development of self-nanoemulsifying drug delivery systems (SNEDDS) containing medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) for augmenting the biopharmaceutical performance of artemether. Equilibrium solubility and pseudoternary phase diagram studies facilitated selection of Captex 355 and Ethyl oleate as MCTs and LCTs, and Cremophor RH 40 and Tween 80 as surfactants, while Transcutol HP as cosolvent for formulating the SNEDDS. Systematic optimization was performed employing the Box-Behnken design taking concentrations of lipid, surfactant and cosolvent as the critical material attributes (CMAs), while evaluating for globule size, emulsification time, dissolution efficiency and permeation as the critical quality attributes (CQAs).

Development and evaluation of ultra-small nanostructured lipid carriers: novel topical delivery system for athlete's foot.

Athlete's foot is a fungal infection of the foot which causes dry, itchy, flaky condition of the skin caused by Trichophyton species. In this study, the potential of ultra-small nanostructured lipid carrier (usNLC)-based topical gel of miconazole nitrate for the treatment of athlete's foot was evaluated. Nanostructure lipid carriers (NLCs) prepared by melt emulsification and sonication technique were characterized for particle size, drug entrapment, zeta potential and drug release.

Effect of apolipoprotein E (APO E) polymorphism on leptin in Alzheimer's disease.

Background: Leptin, a 16 kDa peptide hormone synthesized and secreted specifically from white adipose cells protects neurons against amyloid β-induced toxicity, by increasing Apolipoprotein E (APO E)-dependent uptake of β amyloid into the cells, thereby, protect individuals from developing Alzheimer's disease (AD). The APO E ε4 allele is a known genetic risk factor for AD by accelerating onset. It is estimated that the lifetime risk of developing AD increases to 29% for carriers with one ε4 allele and 9% for those with no ε4 allele.