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Enzymatic oxidations of thiophenes, including thiophene-containing drugs, are important for biodesulfurization of crude oil and drug metabolism of mono- and poly-cyclic thiophenes. Thiophene oxidative dearomatization pathways involve reactive metabolites, whose detection is important in the pharmaceutical industry, and are catalyzed by monooxygenase (sulfoxidation, epoxidation) and dioxygenase (sulfoxidation, dihydroxylation) enzymes. Sulfoxide and epoxide metabolites of thiophene substrates are often unstable, and, while cis-dihydrodiol metabolites are more stable, significant challenges are presented by both types of metabolite. Prediction of the structure, relative and absolute configuration, and enantiopurity of chiral metabolites obtained from thiophene enzymatic oxidation depends on the substrate, type of oxygenase selected, and molecular docking results. The racemization and dimerization of sulfoxides, cis/trans epimerization of dihydrodiol metabolites, and aromatization of epoxides are all factors associated with the mono- and di-oxygenase-catalyzed metabolism of thiophenes and thiophene-containing drugs and their applications in chemoenzymatic synthesis and medicine.

The thiophene-based compounds (such as 4,6-dimethyldibenzothiophene (4,6-DMDBT)) were removed with difficultly that since relatively larger molecules sizes with evident steric hindrance and worse accessibility of active sites during hydrodesulfurization (HDS) reactions. In this study, bimodal pore structure catalysts with higher specific surface areas, larger pore volume and mesoporous diameter were prepared. Moreover, less hydroxyl group in bimodal pore supports cause weaker metal-support interaction (MSI), which further contributes to the formation of Type-II active phase that possesses more active sites. The catalyst activity results of 4,6-DMDBT reveal that the bimodal pore catalyst with a narrow-distributed distribution of mesoporous size (NiMoS/S1) exhibited the highest apparent HDS activity and intrinsic activity for 4,6-dimethyldibenzothiophene. This work can deepen our understanding of the design of catalytic bimodal catalysts with high intrinsic activity and better accessibility of active sites.

In the treatment of patients with acute pulmonary embolism, the efficacy of rivaroxaban, a factor Xa inhibitor, was similar to that of traditional anticoagulation therapy. There was less bleeding in the group receiving rivaroxaban, which supports its use in the treatment of this condition. Pulmonary embolism is a common disease, with an estimated annual incidence of 70 cases per 100,000 population. 1 , 2 The condition usually leads to hospitalization and may recur; it can be fatal. 3 For half a century, the standard therapy for most patients with pulmonary embolism has been the administration of heparin, overlapped and followed by a vitamin K antagonist. 4 , 5 This regimen is effective but complex. 5 – 9 Recently developed oral anticoagulants that are directed against factor Xa or thrombin overcome some limitations of standard therapy, including the need for injection and for regular dose adjustments on the basis of laboratory monitoring. . . .

In this clinical trial, rivaroxaban, an oral factor Xa inhibitor, was effective in the initial and continued treatment of symptomatic venous thromboembolism; it may become part of the treatment armamentarium for this common clinical problem. Acute venous thromboembolism (i.e., deep-vein thrombosis [DVT] or pulmonary embolism) is a common disorder with an annual incidence of approximately 1 or 2 cases per 1000 persons in the general population. 1 , 2 Short-term treatment is effective, with the risk of recurrent disease — the major complication — reduced from an estimated 25% to about 3% during the first 6 to 12 months of therapy. 3 The risk of recurrence remains after treatment ends and can reach 5 to 10% during the first year. 4 , 5 Standard treatment for acute venous thromboembolism is limited by the need for parenteral heparin initially, with overlapping . . .

The strategic design of donor–acceptor (D-A) conjugated porous polymers has emerged as a pivotal methodology for advancing efficient photocatalytic hydrogen evolution. However, conventional D-A polymeric architectures face inherent limitations: excessively strong acceptor units may lower the LUMO energy level, compromising proton (H[sup.+]) reduction capability, while weak D-A interactions result in inadequate light-harvesting capacity and insufficient photogenerated electrons, ultimately diminishing photocatalytic activity. To address these challenges, we developed a new D1-A-D2 conjugated porous polymer (CPP) system. The strategic incorporation of a secondary donor benzothiophene (DBBTh) unit enabled precise bandgap engineering in D[sub.1]-A-D[sub.2] CPPs. Experimental results demonstrate that DBBTh integration significantly enhances both light absorption efficiency and proton reduction ability. Under visible-light irradiation (λ > 420 nm), the Py-BKh1 photocatalyst achieved a hydrogen evolution rate (HER) of 10.2 mmol h[sup.−1] g[sup.−1] with an apparent quantum yield (AQY) of 9.5% at 500 nm. This work provides a groundbreaking paradigm for designing high-performance organic photocatalysts.

In this trial, 14,264 patients with atrial fibrillation were randomly assigned to receive either rivaroxaban or warfarin. In a per-protocol, as-treated analysis, rivaroxaban was noninferior to warfarin with respect to the primary end point of stroke or systemic embolism. Atrial fibrillation is associated with an increase in the risk of ischemic stroke by a factor of four to five 1 and accounts for up to 15% of strokes in persons of all ages and 30% in persons over the age of 80 years. 2 The use of vitamin K antagonists is highly effective for stroke prevention in patients with nonvalvular atrial fibrillation and is recommended for persons at increased risk. 3 – 5 However, food and drug interactions necessitate frequent coagulation monitoring and dose adjustments, requirements that make it difficult for many patients to use such drugs in clinical practice. 6 – 8 Rivaroxaban is . . .

Heterocyclic compounds are attractive candidates because of their vast applications in natural and physical sciences. Thienothiophene (TT) is an annulated ring of two thiophene rings with a stable and electron-rich structure. Thienothiophenes (TTs) fully represent the planar system, which can drastically alter or improve the fundamental properties of organic, π-conjugated materials when included into a molecular architecture. These molecules possessed many applications including, pharmaceutical as well as optoelectronic properties. Different isomeric forms of thienothiophene showed various applications such as antiviral, antitumor, antiglaucoma, antimicrobial, and as semiconductors, solar cells, organic field effect transistors, electroluminiscents etc. A number of methodologies were adopted to synthesize thienothiophene derivatives. In this review, we have addressed different synthetic strategies of various isomeric forms of thienothiophene that have been reported during last seven years, i.e., 2016–2022.

Thiophene derivatives are particularly attractive for application in drug development for their versatile pharmacological properties. We synthesized a series of four compounds with thiophene carboxamide as a scaffold. The structures were established based on HR-MS and 1D- and 2D-NMR. The purity of the compounds was established to be greater than 92% by thin-layer chromatography and NMR. The cytotoxic effects of the newly synthesized compounds were evaluated against the normal HaCaT cell line and A375, HT-29, and MCF-7 cancer cell lines. The cytotoxic assessment revealed that two compounds exhibit a significant cytotoxic effect on all cancer cell lines. To investigate their potential underlying mechanisms of action, several tests were performed: immunofluorescence imaging, caspase-3/7 assay, mitochondrial membrane potential (JC-1) assay, and 2′,7′–dichlorofluorescein diacetate (DCFDA) assay. MB-D2 proved to be the most cytotoxic and effective in terms of caspase 3/7 activation, mitochondrial depolarization and decrease in ROS production; these effects did not occur in normal HaCaT cells, revealing that MB-D2 has a high selectivity against A375 cancer cells.

Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. In vivo , S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Moreover, MCL1 inhibition, either alone or in combination with other anti-cancer drugs, proved effective against several solid cancer-derived cell lines. These results point towards MCL1 as a target for the treatment of a wide range of tumours. S63845 specifically inhibits MCL1 and induces tumour cell death in vitro and in vivo in diverse cancer-derived cell lines with an acceptable safety margin. MCL1 protein as a possible anti-cancer target These authors report the discovery and characterization of a novel inhibitor of the anti-apoptotic pro-survival protein MCL1, which is expressed by multiple tumour types. The compound, termed S63845, activates the BAX/BAK-dependent mitochondrial apoptotic pathway and shows efficacy in several solid tumour models, suggesting that inhibition of MCL1 could be a viable anti-cancer strategy, alone or in combination with other anti-cancer drugs.

Tetrasubstituted 2-acetylthiophene derivative 5 was synthesized and then condensed with various nitrogen nucleophiles such as 5-amino-1,2,4-triazole, 2-aminobenzimidazole, aniline or p-chloroaniline to afford the corresponding iminothiophene derivatives 6–8a,b. Condensation of thiophene 5 with malononitrile as carbon nucleophile afforded compound 9, which underwent nucleophilic addition with DMF-DMA to afford compound 10. The newly synthesized products were characterized by elemental analysis, IR, MS, 1H-13C-NMR and CHN analysis and then evaluated for their antimicrobial activity. Results of the in vitro antibacterial activity showed that thiophene derivative 7 was found to be more potent than the standard drug gentamicin against Pseudomonas aeruginosa. Some of these compounds showed potential antimicrobial activities. Molecular docking and Osiris/Molinspiration analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution with electronic donor group doesn’t guarantee more effective bioactivity. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics.