The 10 most-cited articles in Archiv der Pharmazie, 2023

Abstract In this study, new quinazoline–chromene hybrid compounds were synthesized. The cytotoxic effects on cell viability of the hybrid compounds were tested against A549 human lung adenocarcinoma and BEAS‐2B healthy bronchial epithelial cell lines in vitro. In addition, the ability of the active compounds to inhibit cell migration was tested. Molecular docking studies were performed to evaluate the ligand–protein interactions, and molecular dynamics simulations were performed to determine the interactions and stability of ligand–protein complexes. In silico absorption, distribution, metabolism, and excretion (ADME) studies were conducted to estimate the drug‐likeness of the compounds. Compounds 4 (IC 50 = 51.2 µM) and 5 (IC 50 = 44.2 µM) were found to be the most active agents against A549 cells. They are found to be more selective against A549 cells than the reference drug doxorubicin. They also have the ability to significantly inhibit cell migration. They have the best docking scores against epidermal growth factor receptor (EGFR) (−11.300 and −11.226 kcal/mol) and vascular…

Abstract Eleven novel benzoxazole/benzothiazole‐based thalidomide analogs were designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against HepG‐2, HCT‐116, PC3, and MCF‐7 cells. Generally, the open analogs with semicarbazide and thiosemicarbazide moieties (10, 13a–c, 14, and 17a,b) exhibited higher cytotoxic activities than derivatives with closed glutarimide moiety (8a–d). In particular, compound 13a (IC50 = 6.14, 5.79, 10.26, and 4.71 µM against HepG‐2, HCT‐116, PC3, and MCF‐7, respectively) and 14 (IC50 = 7.93, 8.23, 12.37, and 5.43 µM, respectively) exhibited the highest anticancer activities against the four tested cell lines. The most active compounds 13a and 14 were further evaluated for their in vitro immunomodulatory activities on tumor necrosis factor‐alpha (TNF‐α), caspase‐8 (CASP8), vascular endothelial growth factor (VEGF), and nuclear factor kappa‐B p65 (NF‐κB p65) in HCT‐116 cells. Compounds 13a and 14 showed a remarkable and significant reduction in TNF‐α.…

Abstract Six extracts (water, ethanol, ethanol‐water, ethyl acetate, dichloromethane, and n‐hexane) of Astragalus caraganae were studied for their biological activities and bioactive contents. Based on high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS), the ethanol‐water extract yielded the highest total bioactive content (4242.90 µg g−1), followed by the ethanol and water extracts (3721.24 and 3661.37 µg g−1, respectively), while the least total bioactive content was yielded by the hexane extract, followed by the dichloromethane and ethyl acetate extracts (47.44, 274.68, and 688.89 µg g−1, respectively). Rutin, p‐coumaric, chlorogenic, isoquercitrin, and delphindin‐3,5‐diglucoside were among the major components. Unlike the dichloromethane extracts, all the other extracts showed radical scavenging ability in the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging assay (8.73–52.11 mg Trolox equivalent [TE]/g), while all extracts displayed scavenging property in the 2,2‐azino‐bis(3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS) radical scavenging assay (16.18–282.74…

Merging isatin and arylhydrazone moieties constitutes an efficient strategy to access new potential anticancer derivatives. Consequently, 14 hydrazone-isatin derivatives were synthesized and evaluated for their antiproliferative activity against the NCI-60 cancer cell line panel. A kinase assay demonstrated that compound VIIIb inhibited the epidermal growth factor receptor (EGFR), which was confirmed by docking studies, molecular dynamics, and binding free energy calculations. Further characterizations showed that this compound possesses drug-likeness properties, showed a significant decrease of the cell population in the G2/M phase and led to a significant increase in early and late apoptosis, comparable to erlotinib. Also, VIIIb increased the expression of caspase-3 and Bax and decreased the expression of Bcl-2, confirming its potential as a new proapoptotic compound.

The N-acylhydrazone motif has been shown to be particularly adaptable and promising in the area of medicinal chemistry and drug development, due to its significant biological and pharmacological characteristics. Moreover, N-acylhydrazones are appealing synthetic and biological tools because of their simple and straightforward synthesis. This scaffold has emerged as a fundamental building block for the synthesis of bioactive compounds. Particularly, the N-acylhydrazone scaffold served as a base for the synthesis of a number of potent anticancer agents acting via different mechanisms. An updated summary of the anticancer activity of N-acylhydrazone derivatives described in the literature (from 2017 to 2022) is provided in the current review. It discusses the structure-activity relationship (SAR) of N-acylhydrazone derivatives exhibiting anticancer potential, which could be helpful in designing and developing new derivatives as effective antiproliferative candidates in the future.

As flavin adenine dinucleotide (FAD)-dependent enzymes, monoamine oxidases (MAOs) catalyze the oxidative deamination of various endogenous and exogenous amines. MAO-A inhibitors are thought to be effective therapeutic agents for treating neurological diseases including depression and anxiety. Due to the academic challenge of developing new human (h) MAO-A inhibitors and the potential for discovering substances with remarkable properties compared to existing MAO-A inhibitors, numerous research groups are looking into novel classes of chemical compounds that may function as selective hMAO-A inhibitors. β-Carbolines are reported to be a prominent class of bioactive molecules exhibiting MAO-A inhibition. Chemically, β-carboline is a tricyclic pyrido-3,4-indole ring. It has only recently been discovered that this chemotype has highly effective and specific MAO-A inhibitory activity. In this review, structure-activity relationship studies included in particular research publications from the 1960s to the present are discussed with regard to β-carboline and its analogs. This comprehensive…

Abstract In this study, two diverse series of 2‐aminothiazole‐based multitarget compounds, one propenamide and the other propanamide derivatives, were designed and synthesized. Subsequently, their anticholinesterease and antioxidant (ORAC) activities were tested. Among them, compound 3e was the most potent acetylcholinesterase (AChE) inhibitor (AChE IC 50 = 0.5 μM, butyrylcholinesterase [BChE] IC 50 = 14.7 μM) and compound 9e was the most potent BChE inhibitor (AChE IC 50 = 3.13 μM, BChE IC 50 = 0.9 μM). Kinetic experiments showed that both compounds were mixed‐type inhibitors. According to the anticholinesterease activity results, five compounds ( 3e , 4e , 5e , 9d , and 9e ) were selected for further activity studies, all of which are dual cholinesterase inhibitors. Then, selected compounds were investigated in terms of their metal chelation activity. Moreover, their neuroprotective effects against H 2 O 2 ‐induced damage in the PC12 cell line were evaluated at 10 μM and the results showed that the neuroprotective effect of 3e was 53% compared with the reference ferulic acid…

Abstract A series of 16 novel spirooxindole analogs 8a–p were designed and constructed via cost‐effective single‐step multicomponent [3+2] cycloaddition reaction of azomethine ylide (AY) generated in situ from substituted isatin ( 6a–d ) with suitable amino acids ( 7a–c ) and ethylene‐engrafted pyrazole derivatives ( 5a,b ). The potency of all compounds was assayed against a human breast cancer cell line (MCF‐7) and a human liver cell line (HepG2). Spiro compound 8c was the most active member among the synthesized candidates, with exceptional cytotoxicity against the MCF‐7 and HepG2 cell lines, with IC 50 values of 0.189 ± 0.01 and 1.04 ± 0.21 µM, respectively. The candidate 8c exhibited more potent activity (10.10‐ and 2.27‐fold) than the standard drug roscovitine (IC 50 = 1.91 ± 0.17 µM (MCF‐7) and 2.36 ± 0.21 µM (HepG2)). Compound 8c was investigated for epidermal growth factor receptor (EGFR) inhibition; it exhibited promising IC 50 values of 96.6 nM compared with 67.3 nM for erlotinib. The IC 50 value of 8c (34.98 nM) exhibited cyclin‐dependent kinase 2 (CDK‐2) inhibition,…

The adamantane moiety has attracted significant attention since its discovery in 1933 due to its remarkable structural, chemical, and medicinal properties. This molecule has a notable impact in the therapeutic field because of its "add-on" lipophilicity to any pharmacophoric moieties. As in the case of molecular hybridization, in which one pharmacophore is attached to another one(s) with a probability of increasing the biological activity, adding an adamantane unit improves the absorption distribution, metabolism and excretion properties of the resultant hybrid molecule. This review summarizes various reports highlighting the biological activities of adamantane-based synthetic compounds and their structure-activity relationship study. The information presented in this review may open up possible dimensions for adamantane-based drug development and discovery in the pharmaceutical industry after proper structural modifications.

Abstract Novel thiazolidine‐2,4‐diones have been developed and estimated as conjoint inhibitors of EGFRT790M and VEGFR‐2 against HCT‐116, MCF‐7, A549, and HepG2 cells. Compounds 6a, 6b, and 6c were known to be the dominant advantageous congeners against HCT116 (IC50 = 15.22, 8.65, and 8.80 µM), A549 (IC50 = 7.10, 6.55, and 8.11 µM), MCF‐7 (IC50 = 14.56, 6.65, and 7.09 µM) and HepG2 (IC50 = 11.90, 5.35, and 5.60 µM) mass cell lines, correspondingly. Although compounds 6a, 6b, and 6c disclosed poorer effects than sorafenib (IC50 = 4.00, 4.04, 5.58, and 5.05 µM) against the tested cell sets, congeners 6b and 6c demonstrated higher actions than erlotinib (IC50 = 7.73, 5.49, 8.20, and 13.91 µM) against HCT116, MCF‐7 and HepG2 cells, yet lesser performance on A549 cells. The hugely effective derivatives 4e–i and 6a–c were inspected versus VERO normal cell strains. Compounds 6b, 6c, 6a, and 4i were found to be the most effective derivatives, which suppressed VEGFR‐2 by IC50 = 0.85, 0.90, 1.50, and 1.80 µM, respectively. Moreover, compounds 6b, 6a, 6c, and 6i could interfere with the…