New acetylated flavone C-glycosides from Iris lactea

Chemical investigation of the aerial parts of Iris lactea afforded three new flavone C-glycosides including 4?-O-acetyl-embinin (1), 2?,4?-O-diacetyl-embinin (2) and 6″,4?-O-diacetyl-embinin (3) along with the known analogue embinin (4). Their structures were elucidated by 1D and 2D NMR spectroscopic analysis as well as by HRESIMS data. The sugars were characterized following acid hydrolysis of the respective glycosides and TLC analysis compared to known standards. Duplicated signals can be observed in the NMR spectra, indicating the presence of rotamers caused by rotational hindrance around the glycosyl-flavone CC linkage. All isolated compounds were tested for their antimicrobial and cytotoxic activities but found to be inactive.     

Alum as an efficient catalyst for the multicomponent synthesis of functionalized piperidines

An effective approach to the synthesis of functionalized piperidines via a one-pot multicomponent reaction of aniline, β-ketoester and aldehyde in the presence of alum as an efficient catalyst has been reported. The present procedure offers advantages such as simple workup, short reaction time and offers rapid access to a variety of functionalized piperidines.     

Discovery of New Coumarin-Based Lead with Potential Anticancer,CDK4 Inhibition and Selective Radiotheranostic Effect: Synthesis, 2D & 3D QSAR,Molecular Dynamics,In Vitro Cytotoxicity,Radioiodination, and Biodistribution Studies

Novel 6-bromo-coumarin-ethylidene-hydrazonyl-thiazolyl and 6-bromo-coumarin-thiazolyl-based derivatives were synthesized. A quantitative structure activity relationship (QSAR) model with high predictive power r² = 0.92, and RMSE = 0.44 predicted five compounds; 2b, 3b, 5a, 9a and 9i to have potential anticancer activities. Compound 2b achieved the best ΔG of –15.34 kcal/mol with an affinity of 40.05 pki. In a molecular dynamic study 2b showed an equilibrium at 0.8 Å after 3.5 ns, while flavopiridol did so at 0.5 Å after the same time (3.5 ns). 2b showed an IC₅₀ of 0.0136 µM, 0.015 µM, and 0.054 µM against MCF-7, A-549, and CHO-K1 cell lines, respectively. The CDK4 enzyme assay revealed the significant CDK4 inhibitory activity of compound 2b with IC₅₀ of 0.036 µM. The selectivity of the newly discovered lead compound 2b toward localization in tumor cells was confirmed by a radioiodination biological assay that was done via electrophilic substitution reaction utilizing the oxidative effect of chloramine-t. ¹³¹I-2b showed good in vitro stability up to 4 h. In solid tumor bearing mice, the values of tumor uptake reached a height of 5.97 ± 0.82%ID/g at 60 min p.i. ¹³¹I-2b can be considered as a selective radiotheranostic agent for solid tumors with promising anticancer activity.     

Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2

Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC₅₀ = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC₅₀ 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.     

Synthesis and Characterization of Some New Quinoxalin-2(1H)one and 2-Methyl-3H-quinazolin-4-one Derivatives Targeting the Onset and Progression of CRC with SAR,Molecular Docking,and ADMET Analyses

The pathogenesis of colorectal cancer is a multifactorial process. Dysbiosis and the overexpression of COX-2 and LDHA are important effectors in the initiation and development of the disease through chromosomal instability, PGE2 biosynthesis, and induction of the Warburg effect, respectively. Herein, we report the in vitro testing of some new quinoxalinone and quinazolinone Schiff’s bases as: antibacterial, COX-2 and LDHA inhibitors, and anticolorectal agents on HCT-116 and LoVo cells. Moreover, molecular docking and SAR analyses were performed to identify the structural features contributing to the biological activities. Among the synthesized molecules, the most active cytotoxic agent, (6d) was also a COX-2 inhibitor. In silico ADMET studies predicted that (6d) would have high Caco-2 permeability, and %HIA (99.58%), with low BBB permeability, zero hepatotoxicity, and zero risk of sudden cardiac arrest, or mutagenicity. Further, (6d) is not a potential P-gp substrate, instead, it is a possible P-gpI and II inhibitor, therefore, it can prevent or reverse the multidrug resistance of the anticancer drugs. Collectively, (6d) can be considered as a promising lead suitable for further optimization to develop anti-CRC agents or glycoproteins inhibitors.     

Synthetic analgesics: preparation of racemic 6,7-benzomorphans

A simple preparation of 2-carbomethoxy-2-azabicyclo[3.3.1]nonan-6-one ($\text{7}$ and its conversion to the racemic benzomorphans: $\text{9}$, $\text{10}$, $\text{14}$ are described.     

Transition metal complexes with bidentate ligands spanning trans-positions. XII. The preparation and properties of complexes trans-[MX2 (1)] and trans-[PtHCl (1)] (M = Ni,Pd and Pt; X = Cl and NCS; 1 = ditertiary phosphine)

Complexes [MX₂(1)] (M = Ni, Pd and Pt; X=Cl and NCS; 1 = 2,11-bis(dialkyl-[or diaryl]phosphinomethyl)benzo[c]phenanthrene; alkyl = cyclohexyl t-butyl; aryl = m-tolyl, p-anisyl and m-CF₃ C₆H₄) have been synthesized. An NMR. study of the t-butyl complexes provides evidence for a “fan-like” motion of the benzo[c]phenanthrene moiety over the plane of the complex.     

One-pot synthesis of selenocarbamates from isocyanates and diselenides using the Zn/AlCl3 system

Several N-alkyl/aryl-Se-alkyl/(aryl)selenocarbamates were prepared from various isocyanates and diselenides by reductive cleavage of Se-Se bond with the Zn/AlCl3 system in dry acetonitrile at 80℃.     

Application of the aza-Wittig reaction for efficient synthesis of diversely substituted benzo[f]Chromeno[2,3-d]pyrimidine and benzo[f]chromeno[2,3-d][1,2,4]triazolopyrimidine derivatives

An efficient synthesis of novel benzo[f]Chromeno[2,3-d]pyrimidine and unknown benzo[f]chromeno[2,3-d][1,2,4]triazolopyrimidine derivatives is described utilizing ethyl-2-amino-4-phenyl-4H-benzo[f]chromene-3-carboxylate as precursor via aza-Wittig reaction. The process proved to be simple, high-yielding, and efficient.