This study reports the synthesis and characterization of a novel class of flavonoid acetamide derivatives (FA) of quercetin, apigenin, fisetin, kaempferol, and luteolin. Flavonoids display numerous biological properties but are limited by aqueous insolubility, enzymatic degradation, instability, and low bioavailability. FAs were synthesized, with 80–82% yields, through the sequential modification of the flavonoid hydroxyl groups into the acetamide moieties. Bioavailability, antioxidant, and ADMET are structure–activity-dependent properties that vary across different classes of flavonoids and dictate the prevalent biological applications of the flavonoids. Thus, the FAs were evaluated for their bioavailability, antioxidant, and ADMET toxicity properties versus the unmodified flavonoids (UFs). In vitro bioavailability analysis shows that the UFs have bio-availabilities in the range of 10.78–19.29% against that of the FAs in the range of 20.70–34.87%. The antioxidant capacity was measured using the 2,2-diphenyl-1-picrylhydrazyl (DPPH·) assay with recorded IC₅₀ values of 2.19–13.03 μM for the UFs. Conversely, the FAs had high DPPH IC₅₀ values ranging from 33.83 to 67.10 μM and corresponding to lower antioxidant activity. The FAs showed favorable ADMET properties. The modification of flavonoids into FAs significantly improves the bioavailability and the ADMET toxicity properties, albeit with decreased antioxidant activity. This work highlights the effect of the global modification of the flavonoids with the acetamide groups on the bioavailability, antioxidant, and ADMET toxicity properties which are critical determinants in the biological applications of the flavonoids.

In this work, eight new 1,2,3-triazoles (6a–h) were synthesized from acetylenes’ “click” reaction with p-substituted azide derivatives. The structures of the compounds were characterized using standard analytical and spectroscopic methods (elemental analysis, FT-IR, ¹H(¹³C)NMR). The anticancer, antioxidant, α-amylase, ADME, molecular docking studies of synthesized triazoles were investigated. According to α -amylase enzyme inhibition results, all compounds except 6c (IC₅₀: 2299 μg/mL) were found to have a higher IC₅₀ value than the standard drug acarbose (IC₅₀: 891 μg/mL). Compound 6g (IC₅₀: 68 μg/mL) exhibited 13 times higher activity than standard acarbose. All compounds, except 6e, have been shown to have greater DPPH radical scavenging capabilities than BHT and β-carotene standards. According to ABTS radical scavenging studies, all compounds showed higher scavenging activity than ascorbic acid and Trolox. To determine the anticancer activity of the synthesized compounds, they were screened against the Hela cell line, and the results were compared with standard cisplatin (IC₅₀: 16.30 μg/mL). Compound 6a (IC₅₀: 49.03 μg/mL) was determined to have moderate activity relative to cisplatin. The compounds were examined comprehensively for ADME characteristics and did not violate any drug-likeness rule. ADME data showed that all physicochemical and pharmacological parameters of the compounds remained within defined limits as specified in Lipinski's rules (RO5) and put forth a high bioavailability profile. The molecular docking findings show that all molecules have a high affinity by exhibiting polar and apolar contact with essential residues in the binding pocket of α-amylase. Communicated by Ramaswamy H. Sarma

New hybrid compounds belonging to the class of 1,4-disubstituted 1,2,3-triazoles were synthesized. The structural characterization of the synthesized compounds was performed using IR, ¹H-NMR, ¹³C NMR and elemental analysis techniques. Diarylketones 1a and 1b were used as starting compounds for the synthesis of triazoles. The corresponding diarylmethanol derivatives (2a,b) were obtained from reduction of ketone units with NaBH₄. Oxyalkynes (3a,b) were obtained by treating the hydroxyl group with NaH in anhydrous THF and then with propargylbromide. The target hybrid structures 6a-n were obtained from the metal-catalyzed "click reaction" of the arylazide and alkyne units. The newly synthesized compounds were structurally analysed using ¹H-NMR, ¹³C-NMR, elemental analysis, LC-MS and FT-IR. The antioxidant and anticancer activities of all compounds were investigated. It has been determined that the new hybrid structures have very good antioxidant and anticancer activities according to the standards. In particular, compounds 6b, 6h, 6i and 6j (IC₅₀: 1.87, 12.5, 7.22, 8.04 µM) showed excellent activity compared to standard 5-Fu (IC₅₀: 40.89 µM). According to the results of molecular docking of compounds 6b and 6i with the highest cancer activity, MetAP-2 was found to have a high affinity through exposed polar and apolar contacts with fundemental residues in the binding pocket. Communicated by Ramaswamy H. Sarma