Synthesis and bioactivity evaluation of eugenol hybrids obtained by Mannich and 1,3 dipolar cycloaddition reactions

Abstract

Design, synthesis, and bioactivity evaluation of novel mannich bases (2a-2j) and triazole-chalcone derivatives (7a-7k) of Eugenol 1 were reported. Among all the derivatives tested for antiproliferative activity, di-amine manich derivative 2b (32.92 μM), and 4-methoxy chalcone triazole derivative 7d (33.05 μM) significantly inhibited HepG2 cell lines when compared to the standard doxorubicin (37.29 μM). Whereas most of the compounds such as diethylamine 2a (17.75 μM), (aminomethyl) methane diamine 2b (17.02 μM), and bis (chloromethyl) amine 2c (20.12 μM) showed moderate to better inhibition towards MCF-7 cell lines. The synthesized analogues were also tested for antidiabetic and antiobesity potentials. Compounds 2f (55.50%), 2c (54.34%), 7g (55.5%), and 2a (55.5%) have shown moderate inhibitory potentials toward intestinal α-glucosidase enzyme when compared to the standard Acarbose (72.86%). Likewise, compounds 7d (82.95%), 7f (76.19%), 7g (74.81%), 7e (74.81%), and 2g (72.50%) have shown significant to moderate inhibitory potentials toward Pancreatic lipase enzyme when compared to the standard orlistat (91.10%). ROS induces life-threatening diseases like diabetes, cancer, etc., and antioxidants play a major role in controlling their production. Compounds 2c (99.81%), 2i (99.80%), 2d (99.26%), 2g (98.79%), and 2f (98.42%) have shown significant antioxidant profiles in ABTS assay when compared to the standard Trolox (99.07%). Further, In silico Molecular docking and pharmacokinetic screening of the eugenol derivatives complemented the in vitro results indicating the drug likeness of the obtained active compounds.

Anticancer Activity of Mannich Bases: A Review of Recent Literature

“…Phenolic Mannich bases of simple phenols have been also evaluated as anticancer agents. Out of ten Mannich bases of eugenol, compound 55 (NR 2 =N(CH 2 NH 2 ) 2 ) (Figure 8) had a broad antiproliferative activity against A549, HepG2, MCF‐7 and SK‐OV‐3 cell lines used in the study, and was more potent (IC 50 =33 μM) than doxorubicin against HepG cells [69] . Aminomethylation of hydroxychavicol took place at the least…”

“…Out of ten Mannich bases of eugenol, compound 55 (NR 2 = N(CH 2 NH 2 ) 2 ) (Figure 8) had a broad antiproliferative activity against A549, HepG2, MCF-7 and SK-OV-3 cell lines used in the study, and was more potent (IC 50 = 33 μM) than doxorubicin against HepG cells. [69] Aminomethylation of hydroxychavicol took place at the least [70] Depending on the nature of the amine reagent, aminomethylation of thymol occurred either ortho or para to the hydroxyl group to give two series of Mannich bases 57 and 58 (Figure 8), whose evaluation against Ca9-22, HSC-2, HSC-3 and HSC-4 human oral squamous carcinoma cell lines showed that they generally had moderate to poor cytotoxicity (CC 50 > 50 μM). [71] Mannich bases 59 (Figure 8) were prepared from structurally diverse phenols as substrates and ciprofloxacin as amine reagent, and their evaluation towards multiple cancer cell lines at National Cancer Institute showed that aminomethylated 1-and 2-naphthols were the most potent in this series against many of the tested cell lines.…”

Synthesis, Antioxidant and Antituberculosis Evaluation of Eugenol Derivatives from Mannich Condensation

“…No improvement in the antiradical activity of compounds 1, 2 and 4, while eugenol methylpiperazine 3 experienced a decrease in activity compared to eugenol (Table 1). Buduma et al [2] have recently reported the synthesis and antiradical property of compounds 2, 3 and 5. Derivative 3 showed better DPPH scavenging of 64.15 %, at 10 μg/mL, as well as better ABTS scavenging of 98.79 %, at 25 μg/mL.…”

Recent advances in biological applications of mannich bases — An overview

“…When synthetic eugenol derivatives were tested in vitro for their ability to inhibit pancreatic lipase, compound 59) also exhibited moderate antilipase activity. 1 The structures of these compounds are given in Figure 11.…”

“…Mannich bases and their derivatives are being developed with the aim of improving their physicochemical and druglike characteristics, which may have greater influence over pharmacological applications. [1][2][3] Many bioactivities, such as antineoplastic, diuretic, antipsychotic, anticonvulsant, centrally acting muscle relaxant, antibacterial and antiviral ones, are present in https://doi.org/10.18231/j.ijpca.2023.004 2394-2789/© 2023 Innovative Publication, All rights reserved. 15 the Mannich base of heterocyclic compounds.…”