Synthesis, Biological Assessment, and Structure Activity Relationship Studies of New Flavanones Embodying Chromene Moieties

Abstract

Novel flavanones that incorporate chromene motifs are synthesized via a one-step multicomponent reaction. The structures of the new chromenes are elucidated by using IR, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and elemental analysis. The new compounds are screened for their in vitro antimicrobial and cytotoxic activities. The antimicrobial properties are investigated and established against seven human pathogens, employing the agar well diffusion method and the minimum inhibitory concentrations. A majority of the assessed derivatives are found to exhibit significant antimicrobial activities against most bacterial strains, in comparison to standard reference drugs. Moreover, their cytotoxicity is appraised against four different human carcinoma cell lines: human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and adenocarcinoma human alveolar basal epithelial cell (A-549). All the desired compounds are subjected to in-silico studies, forecasting their drug likeness, bioactivity, and the absorption, distribution, metabolism, and excretion (ADME) properties prior to their synthetic assembly. The in-silico molecular docking evaluation of all the targeted derivatives is undertaken on gyrase B and the cyclin-dependent kinase. The in-silico predicted outcomes were endorsed by the in vitro studies.

Design, Synthesis, Molecular Modeling, Anticancer Studies, and Density Functional Theory Calculations of 4-(1,2,4-Triazol-3-ylsulfanylmethyl)-1,2,3-triazole Derivatives

“…Furthermore, the speed and accuracy of the molecular docking approaches have been enhanced and these methods now play a noteworthy role in structure-based drug design. The newly synthesized hybrids were gauged using in silico docking studies for acquiring an additional apprehension of the binding pattern of the target ligands with the cyclin-dependent kinase 2 (CDK2), whose overexpression causes dysfunction of the cell cycle, which is thoroughly allied with hyperproliferation of cancer cells. − Numerous evidences have been put forward in the literature sustaining the concept of restraining cancer progression by aiming CDK2. − In various categories of human tumors, the dysregulation of CDK2 is noticed, thereby for anticancer therapy, making CDK2 a promising drug target. ,− In breast cancer progression, CDK2 is considered accountable for activating and phosphorylating the receptor hormones. CDK2 structure with Protein Data Bank (PDB) ID: 2R3I was recruited for carrying out molecular docking studies owing to its higher resolution (1.28 Å) and nonmutated monomeric form.…”

Novel quinazoline–chromene hybrids as anticancer agents: Synthesis, biological activity, molecular docking, dynamics and ADME studies

“…Compounds Q14-15 were synthesized by treating the amide obtained from the reaction of methyl anthranilate with chloroacetyl chloride first with the corresponding secondary amines and then with hydrazine hydrate. Finally, 15 new chromen-4(4H)-one-quinazolin-4(3H)-one hybrids (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were obtained from the reaction of 4-oxo-4H-chromene-3-carbaldehyde with compounds Q1-15 in the glacial acetic acid as solvent (Scheme 1). The structures of the target novel compounds were characterized by fourier transform infrared (FTIR), 1 H nuclear magnetic resonance ( 1 H NMR), 13 C nuclear magnetic resonance (attached proton test) 13 C NMR (APT), and high resolution mass spectrometry (HRMS) spectroscopic techniques.…”

“…This ring system is known as a privileged pharmacophore due to its ability to readily interact with a wide range of biological targets, and it is often used as a scaffold for the development of new drugs. [ 9,10 ] Chromene compounds have been found to have a wide range of biological activities, including anticancer, [ 11 ] anti‐inflammatory, [ 12 ] antiviral, [ 13 ] antioxidant, [ 14 ] antibacterial, [ 15 ] and anticholinergic [ 16 ] properties. Because of its wide range of pharmacological properties, the research on chromene and compounds containing chromene moiety has grown exponentially and found to be an important area of research in medicinal and pharmaceutical chemistry.…”

“…This ring system is known as a privileged pharmacophore due to its ability to readily interact with a wide range of biological targets, and it is often used as a scaffold for the development of new drugs. [9,10] Chromene compounds have been found to have a wide range of biological activities, including anticancer, [11] anti-inflammatory, [12] antiviral, [13] antioxidant, [14] antibacterial, [15] and anticholinergic [16] properties.…”

2H/4H-Chromenes—A Versatile Biologically Attractive Scaffold

“…Among them, compound 61 exhibited remarkable potency toward all targeted cell lines in the range of IC 50 1.08–2.42 μg/mL. It is needed to discover the action mechanism of molecule 61 and to develop an effective lead molecule for the treatment of cancer (Assirey et al, 2020 ).…”