Design, Synthesis, and Biological Evaluation of New Selective PDE4 Inhibitors for Topical Treatment of Psoriasis.

Psoriasis is a complex and chronic inflammatory disease. Current drugs help control the symptoms of psoriasis but make no cure, urging discovery of novel drugs. We report in this paper the discovery of new phosphodiesterase 4 (PDE4) inhibitors for treatment of psoriasis.

Development of selective heterocyclic PDE4 inhibitors for treatment of psoriasis.

Psoriasis is a chronic autoimmune disease that badly affects the life quality of patients and their families. Inadequate efficacy, safety risks, high cost and low compliance of current psoriasis drugs urge development of novel small molecular drugs. In this study, two series of 37 novel compounds were designed and synthesized as inhibitors of phosphodiesterase 4 (PDE4) that specifically hydrolyzes second messenger cAMP and is an effective target for treatment of inflammatory diseases.

One-pot sequential synthesis of unsymmetrical diarylmethanes using methylene chloride as a C1-synthon.

Bisindolylmethane (BIM) and its derivatives are widely used in the pharmaceutical industry due to their significant biological activities. However, most reported synthetic methods are focused on the synthesis of symmetric BIMs, while the synthesis of unsymmetrical BIMs remains a challenge. Herein, an unprecedented two-step one-pot method to afford unsymmetrically substituted 3,3'-BIM frameworks, using methylene chloride (DCM) as the C1-synthon is reported.

Covalent Organic Framework-Based Theranostic Platforms for Restricting H1N1 Influenza Virus Infection.

Background: Influenza A (H1N1) virus is a highly contagious respiratory disease that causes severe illness and death. Vaccines and antiviral drugs are limited by viral variation and drug resistance, so developing efficient integrated theranostic options appears significant in anti-influenza virus infection.

Methods: In this study, we designed and fabricated covalent organic framework (COF) based theranostic platforms (T705@DATA-COF-Pro), which was composed of an RNA polymerase inhibitor (favipiravir, T705), the carboxyl-enriched COF (DATA-COF) nano-carrier and Cy3-labeled single DNA (ssDNA) probe.

Anticancer efficacy triggered by synergistically modulating the homeostasis of anions and iron: Design, synthesis and biological evaluation of dual-functional squaramide-hydroxamic acid conjugates.

Targeting the homeostasis of anions and iron has emerged as a promising therapeutic approach for the treatment of cancers. However, single-targeted agents often fall short of achieving optimal treatment efficacy. Herein we designed and synthesized a series of novel dual-functional squaramide-hydroxamic acid conjugates that are capable of synergistically modulating the homeostasis of anions and iron.

Divergent synthesis of difluoromethylated indole-3-carbinols, bisindolylmethanes and indole-3-methanamines.

Indole-3-carbinol, bisindolylmethanes (BIMs) and indole-3-methanamines exhibit diverse therapeutic activities. Fluorinated molecules are widely used in pharmaceuticals. Herein we report a facile and straightforward method for the successful synthesis of difluoromethylated indole-3-carbinols, bisindolylmethanes and indole-3-methanamines by a Friedel-Crafts reaction.

Design, synthesis and anti-inflammatory activity study of lansiumamide analogues for treatment of acute lung injury.

Acute lung injury (ALI) is an inflammation-mediated respiratory disease with a high mortality rate. Medications with anti-inflammatory small molecules have been demonstrated in phase I and II clinical trials to considerably reduce the ALI mortality. In this study, two series of lansiumamide analogues were designed, synthesized, and evaluated for anti-inflammatory activity for ALI treatment.

The Clinical Efficacy of Autologous Platelet-Rich Plasma Interventional Circulatory Perfusion Combined with Radiofrequency Ablation and Thermocoagulation in the Treatment of Discogenic Low Back Pain.

Objective: In this study, we aimed to explore the efficacy of the autologous platelet-rich plasma (PRP) interventional circulatory perfusion combined with radiofrequency ablation and thermocoagulation (RFAT) in the treatment of discogenic low back pain (DLBP).

Methods: From January 2020 to November 2022, 158 patients of the Second Affiliated Hospital of Nanchang University were selected as the study subjects, and 24 patients met the exclusion criteria. The 134 patients who met the inclusion criteria were divided into 65 patients in the control group (3 patients lost to follow-up) and 69 patients in the observation group (5 patients lost to follow-up), so 126 patients were actually completed the study, including 62 patients in the control group and 64 patients in the observation group.

Bicyclic Amidine-Triggered Cyclization of -Alkynylisocyanobenzenes: Synthesis of Lactam-Derived Quinolines.

Efficient access to the synthesis of lactam-derived quinoline through a bicyclic amidine-triggered cyclization reaction from readily prepared -alkynylisocyanobenzenes has been developed. The reaction was initiated by nucleophilic attack of the bicyclic amidines to -alkynylisocyanobenzenes, subsequently with intramolecular cyclization to produce a DBU-quinoline-based amidinium salt, followed by hydrolysis to afford the lactam-derived quinoline in moderate to good yields.

Facile access to 2-hydroxy-2-substituted indole-3-ones a copper-catalyzed oxidative cyclization of 2-arylethynylanilines.

This paper reports a practical and versatile oxidative cyclization of 2-arylethynylanilines towards 2-hydroxy-2-substituted indol-3-ones a copper-catalyzed radical approach in the presence of O. The transformation of 2-hydroxy-2-arylindol-3-ones to 3-hydroxy-3-arylindol-2-ones proceeds well with good yields and highlights the practicability and utility of this catalytic system. Mechanistic investigations showed that the acetyl substituent on 2-arylaethynylanilines played an important role in the formation of the cyclic products and the reaction proceeded an -center radical-based aza-cyclization pathway.

Design, synthesis, and evaluation of 2,2'-bipyridyl derivatives as bifunctional agents against Alzheimer's disease.

Alzheimer's disease (AD) is a complex multifactorial neurodegenerative disease. Metal ion dyshomeostasis and Aβ aggregation have been proposed to contribute to AD progression. Metal ions can bind to Aβ and promote Aβ aggregation, and ultimately lead to neuronal death.

Design, synthesis, and biological evaluation of diaryl heterocyclic derivatives targeting tubulin polymerization with potent anticancer activities.

A series of diaryl heterocyclic analogues were designed and synthesized as tubulin polymerization inhibitors. Among them, compound 6y showed the highest antiproliferative activity against HCT-116 colon cancer cell line with an IC values of 2.65 μM.

Synthesis of α-Boryl Ketones via Hydration or Oxidation of B(MIDA)-Decorated Alkynes.

α-Boryl ketones are traditionally challenging targets in organic synthesis. Reported herein is a mild and metal-free synthesis of α-boryl ketones via the hydration or oxidation of -methyliminodiacetyl boronate (B(MIDA))-decorated alkynes. A new hydration system comprised of AcCl and HO in HFIP allows the hydration of arylethynyl B(MIDA)s at room temperature with decent functional group tolerance.

Design, Synthesis and Antitumor Activity of Novel Selenium-Containing Tepotinib Derivatives as Dual Inhibitors of c-Met and TrxR.

Cellular mesenchymal-epithelial transition factor (c-Met), an oncogenic transmembrane receptor tyrosine kinase (RTK), plays an essential role in cell proliferation during embryo development and liver regeneration. Thioredoxin reductase (TrxR) is overexpressed and constitutively active in most tumors closely related to cancer recurrence. Multi-target-directed ligands (MTDLs) strategy provides a logical approach to drug combinations and would adequately address the pathological complexity of cancer.

Cp*Ir(III) and Cp*Rh(III)-catalyzed annulation of salicylaldehydes with fluorinated vinyl tosylates.

A mild, selective and redox-neutral Cp*Ir(III)- and Cp*Rh(III)-catalyzed C-H activation/annulation of salicylaldehydes with fluorovinyl tosylates is reported. The use of monofluorovinyl tosylate favors the synthesis of C2- and C3-substitution-free chromones C-H activation/β-F elimination/annulation, whereas difluorovinyl tosylate leads to the construction of C2-fluoroalkoxy chromones. Mild reaction conditions and good functional-group tolerance were observed.

Access to 3-Amino-[1,2,4]-triazolo Pyridines and Related Heterocycles via Electrochemically Induced Desulfurative Cyclization.

An efficient, one-pot approach has been established for synthesizing a wide range of 3-amino-[1,2,4]-triazolo pyridines and related heterocycles from the electrochemically induced desulfurative cyclization of 2-hydrazinopyridines with isothiocyanates. The protocol allows for the formation of C-N bonds under simple conditions without transition metals or external oxidants. The practicability of this strategy is demonstrated by its broad substrate scope, good functional group compatibility, and gram-scale synthesis.

Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease.

Fifteen chalcone derivatives 3a-3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aβ aggregation effectively ranged from 45.9-94.

Design, synthesis and biological evaluation of indole-based [1,2,4]triazolo[4,3-a] pyridine derivatives as novel microtubule polymerization inhibitors.

A series of indole-based [1,2,4]triazolo [4,3-a]pyridine derivatives was designed and synthesized as novel microtubulin polymerization inhibitors by using a conformational restriction strategy. These compounds exhibited moderate to potent anti-proliferative activities against a panel of cancer cell lines (HeLa, A549, MCF-7 and HCT116). Among them, compound 12d featuring a N-methyl-5-indolyl substituent at the C-6 position of the [1,2,4]triazolo [4,3-a]pyridine core exhibited the highest antiproliferative activity with the IC values ranging from 15 to 69 nM, and remarkable inhibitory effect on tubulin polymerization with an IC value of 1.

Photochemical Radical C-H Halogenation of Benzyl N-Methyliminodiacetyl (MIDA) Boronates: Synthesis of α-Functionalized Alkyl Boronates.

α-Haloboronates are useful organic synthons that can be converted to a diverse array of α-substituted alkyl borons. Methods to α-haloboronates are limiting and often suffer from harsh reaction conditions. Reported herein is a photochemical radical C-H halogenation of benzyl N-methyliminodiacetyl (MIDA) boronates.

A porcine alveolar macrophage cell line stably expressing CD163 demonstrates virus replication and cytokine secretion characteristics similar to primary alveolar macrophages following PRRSV infection.

The in vitro investigation of cytokine secretion induced by porcine reproductive and respiratory syndrome virus (PRRSV) requires porcine alveolar macrophages (PAMs) and their interaction with immunocytes. However, immortalized monoclonal PAMs (mPAMs) are non-permissive for PRRSV infection. The porcine CD163 receptor isolated from primary PAMs (pPAMs) confers susceptibility to PRRSV infection; thus, this approach could be used to establish a novel cell line to facilitate the exploration of PRRSV infection kinetics.