New Natural Eugenol Derivatives as Antiproliferative Agents: Synthesis, Biological Evaluation, and Computational Studies

Abstract

Semisynthetic modifications of natural products have bestowed us with many anticancer drugs. In the present work, a natural product, eugenol, has been modified synthetically to generate new anticancer agents. The final compounds were structurally confirmed by NMR, IR, and mass techniques. From the cytotoxicity results, compound 17 bearing morpholine was found to be the most active cytotoxic agent with IC 50 1.71 (MCF-7), 1.84 (SKOV3), and 1.1 μM (PC-3) and a thymidylate synthase (TS) inhibitor with an IC 50 of 0.81 μM. Further cellular studies showed that compound 17 could induce apoptosis and arrest the cell cycle at the S phase in PC-3 carcinoma. The docking study strongly favors compound 17 to be a TS inhibitor as it displayed a similar interaction to 5-fluorouracil. The in silico pharmacokinetics and DFT computational studies support the results obtained from docking and biological evaluation and displayed favorable pharmacokinetic profile for a drug to be orally available. Compound 17 was found to be a promising TS inhibitor which could suppress DNA synthesis and consequently DNA damage in prostate cancer cells.

Synthesis of Flurbiprofen Based Amide Derivatives as Potential Leads for Diabetic Management: In Vitro α‐glucosidase Inhibition, Molecular Docking and DFT Simulation Approach

“…The molecular electrostatic potential (MEP), in the qualitative interpretation of chemical reactivity has a long history [45] . That can provide useful insights into the reactivity and selectivity of chemical reactions [46] .…”

“…The molecular electrostatic potential (MEP), in the qualitative interpretation of chemical reactivity has a long history. [45] That can provide useful insights into the reactivity and selectivity of chemical reactions. [46] It shows the spatial variation of electrostatic potential around a molecule, which reflects the electronic structure and shape of the molecule.…”

Synthesis and Characterization of a New Class of Chromene-Azo Sulfonamide Hybrids as Promising Anticancer Candidates with the Exploration of Their EGFR, hCAII, and MMP-2 Inhibitors Based on Molecular Docking Assays

“…The docking analysis was performed to explicate the potency of these desirable molecules in vitro against the EGFR, MMP-2, and hCAII proteins, respectively, through their potential interaction mechanisms with their crystal frameworks (PDB: 4HJO [77], 1HOV [78], 3M04 [79]). The docking investigation procedures were implemented using Glide's module ® [80][81][82][83][84]. The preliminary inhibitors (Erlotinib, hydroxamic acid, and sulfonamide) were redocked into the examined crystal frameworks to verify the docking methodology.…”

Synthesis, characterization, and inhibition effects of a novel eugenol derivative bearing pyrrole functionalities on the corrosion of mild steel in a HCl acid solution

“…16–18 To synthesize eugenol-based heterocyclic derivatives with interesting activities, Syed Nazreen's team developed new 1,3,4-oxadiazole heterocycles with anticancer properties. 19 Similarly, Abdelmaoujoud Taia and colleagues have synthesized new heterocycles, 1,2,3-triazoles, with anticorrosive activity, particularly for iron in acid solutions. 20 Moreover, heterocyclic pyrrole compounds, characterized by a five-membered ring comprising four adjacent carbon atoms and one nitrogen atom, have recently been prepared by Sergei Boichuk et al 21 These products have found wide therapeutic applications 21,22 due to their diverse biological properties, 23 including antimicrobial 24 and anticancer activities.…”