Bioevaluation of synthetic pyridones as dual inhibitors of α-amylase and α-glucosidase enzymes and potential antioxidants

Herein, a library of novel pyridone derivatives 1–34 was designed, synthesized, and evaluated for α-amylase and α-glucosidase inhibitory as well as antioxidant activities. Pyridone derivatives 1–34 were synthesized via a one-pot multi-component reaction of variously substituted aromatic aldehydes, acetophenone, ethyl cyanoacetate, and ammonium acetate in absolute ethanol. Synthetic compounds 1–34 were structurally characterized by different spectroscopic techniques. Most of the tested compounds showed more promising inhibition potential than the standard acarbose (IC₅₀ = 14.87 ± 0.16 µM) but compounds 13 and 12 were found to be the most potent compounds with IC₅₀ values of 9.20 ± 0.14 µM and 3.05 ± 0.18 µM against α-amylase and α-glucosidase enzymes, respectively. Compounds 1–34 also displayed moderate antioxidant potential in the range of IC₅₀ = 96.50 ± 0.45 to 189.98 ± 1.00 µM in comparison to the control butylated hydroxytoluene (BHT) (IC₅₀ = 66.50 ± 0.36 µM), in DPPH radical scavenging activities. Additionally, all synthetic derivatives were subjected to a molecular docking study to investigate the interaction details of compounds 1–34 (ligands) with the active site of enzymes (receptors). These results indicate that the newly synthesized pyridone class may serve as promising lead candidates for controlling diabetes mellitus and as antioxidants.     

Design and synthesis of novel 1,2,3,4-tetrazines as new anti-leukemia cancer agents

A series of novel 1,2,3,4-tetrazines were designed and synthesized. ¹H-NMR spectroscopy, ¹³C NMR spectroscopy, and HRMS were used to determine the structures of this novel compounds. Computational approaches suggested that DHFR is a putative target for the newly synthesized 11 compounds. Extensive molecular dynamics simulations followed by molecular docking simulations were employed to evaluate DHFR as a potential target protein. The anticancer activities of the compounds were evaluated against five different types of leukemia cell lines (Jurkat, Nalm-6, Reh, K562, and Molt-4) and one non-leukemic cell line (Hek293T) by MTT test in vitro and imatinib was used as a control drug. Among these compounds, 3a exhibited the best activity against all the leukemic cell lines, except Reh cell line. For Nalm-6, K562, Jurkat, and Molt-4 cell lines, IC₅₀ values were found to be 15.98, 19.12, 23.15, and 25.80 μM, respectively. Our work focuses on the synthesis of original and novel 1,2,3,4-tetrazine derivatives while contributing to the ongoing effort to discover more potent new antileukemia agents.