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The design and synthesis of novel cytotoxic agents is still an interesting topic for medicinal chemistry researchers due to the unwanted side effects of anticancer drugs. In this study, a novel series of uracil-azole hybrids were designed and synthesized. The cytotoxic activity, along with computational studies: molecular docking, molecular dynamic simulation, density functional theory, and ADME properties were also, evaluated. The compounds were synthesized by using 3-methyl-6-chlorouracil as the starting material. Cytotoxicity was determined using MTT assay in the breast carcinoma cell line (MCF-7) and Hepatocellular carcinoma cell line (HEPG-2). These derivatives demonstrated powerful inhibitory activity against breast and hepatocellular carcinoma cell lines in comparison to Cisplatin as positive control. Among these compounds, 4j displayed the best selectivity profile and good activity with IC 50 values of 16.18 ± 1.02 and 7.56 ± 5.28 µM against MCF-7 and HEPG-2 cell lines respectively. Structure-activity relationships revealed that the variation in the cytotoxic potency of the synthesized compounds was affected by various substitutions of benzyl moiety. The docking output showed that 4j bind well in the active site of EGFR and formed a stable complex with the EGFR protein. DFT was used to investigate the reactivity descriptors of 4a and 4j. The outputs demonstrated that these uracil-azole hybrids can be considered as potential cytotoxic agents., (© 2023. The Author(s).)

Herein, we reported the synthesis of nineteen novel 1,2,4-triazole derivatives including 1,3-diphenyl-2-(1H-1,2,4-triazol-1-yl) propan-1-ones (7a-e), 1-(1,3-diphenylpropan-2-yl)-1H-1,2,4-triazole (8a-c) and 1,4-diphenyl-2-(1H-1,2,4-triazol-1-yl) butane-1,4-diones (10a-k). The structures of these derivatives were confirmed by spectroscopic techniques like IR, 1 H-NMR, Mass spectroscopy and Elemental analysis. The cytotoxic activities of the synthesized compounds were evaluated against three human cancer cell lines including MCF-7, Hela and A549 using MTT assay. Compounds 7d, 7e, 10a and 10d showed a promising cytotoxic activity lower than 12 μM against Hela cell line. The safety of these compounds was also, evaluated on MRC-5 as a normal cell line and relieved that most of the synthesized compounds have proper selectivity against normal and cytotoxic cancerous cell lines. Finally, molecular docking studies were also, done to understand the mechanism and binding modes of these derivatives in the binding pocket of aromatase enzyme as a possible target., (© 2022. The Author(s).)

A novel series of diphenylquinoxaline-6-carbohydrazide hybrids 7a-o were rationally designed and synthesized as anti-diabetic agents. All synthesized compounds 7a-o were screened as possible α-glucosidase inhibitors and exhibited good inhibitory activity with IC 50 values in the range of 110.6 ± 6.0 to 453.0 ± 4.7 µM in comparison with acarbose as the positive control (750.0 ± 10.5 µM). An exception in this trend came back to a compound 7k with IC 50 value > 750 µM. Furthermore, the most potent derivative 7e bearing 3-fluorophenyl moiety was further explored by kinetic studies and showed the competitive type of inhibition. Additionally, the molecular docking of all derivatives was performed to get an insight into the binding mode of these derivatives within the active site of the enzyme. In silico assessments exhibited that 7e was well occupied in the binding pocket of the enzyme through favorable interactions with residues, correlating to the experimental results., (© 2022. The Author(s).)

A series of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines (S 1 -S 11 ) were synthesized with an eco-friendly and recoverable nanocatalyst (GO-Fe 3 O 4 -Ti (IV) ) as an efficient magnetic composite. The new nanocatalyst was characterized by FT-IR, XRD and, EDS analysis. A conformable procedure, easy to work up and having a short reaction time with high yields are some advantages of this method. The new catalyst is also thermal-stable, reusable and, environment-friendly. The chemical structures of the synthesized 1,3-oxazine compounds were confirmed by comparing their melting points with those reported in literature. Then, the anticonvulsant activity of these compounds was assessed by the intraperitoneal pentylenetetrazole test (ipPTZ). Compounds S 10 and S 11 displayed considerable activity against chemically-induced seizure tests. The molecular simulation was also done to achieve their binding affinities as γ-aminobutyric acid A (GABA-A) receptor agonists as an assumptive mechanism of their anticonvulsant action. The result of molecular studies represented strongly matched with biological activity. Molecular docking simulation of the potent compound (S 10 ) and diazepam as the positive control was performed and some critical residues like Thr262, Asn265, Met286, Phe289, and Val290 were identified. Based on the anticonvulsant results and also in silico ADME predictions, S 11 can be to become a potential drug candidate as an anticonvulsant agent., (© 2022. The Author(s).)

Background: Artemisia splendens from the Asteraceae family is a new source of biologically active compounds. The current study investigated to evaluate antimicrobial and cytotoxicity activity of methanolic extracts and their fractions obtained from aerial parts by agar disk diffusion and MTT methods, respectively. The active fractions were subjected to preparative HPLC for isolating the pure compounds, which were structurally elucidated, by 1 H and 13 C NMR., Results: The results showed that the methanolic extract and its 60% SPE fraction have the anti-proliferative activity on A549 cell line in comparison with the control group. Meanwhile, the methanolic extract and its 40% SPE fraction can inhibit the growth of Gram-positive strains as anti-microbial activity. The 60% SPE fraction also illustrated anti-proliferative activity on the HT-29 cell line compared to the control group. Chromatographic separations via preparative HPLC yielded 5 flavonoids and three flavonoid glycosides., Conclusion: Based on the results it can be concluded that A. splendens as a potential source of cytotoxic and antimicrobial compounds can be used in pharmaceutics.