Dihydroquinoline derivative as a potential anticancer agent: synthesis, crystal structure, and molecular modeling studies (original) (raw)
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Eclética Química, 2023
Lung carcinoma (LC) is responsible for almost one- third of all cancer fatalities worldwide. Tetrahydroquinoline is an organic molecule that is the semi-hydrogenated derivative of quinoline and could be found in several naturally occurring compounds such as flindersine, oricine etc. Some tetrahydroquinoline derivatives with pyrazole and hydrazide moieties were evaluated in silico against A549 (human lung cancer cell lines). The quantitative structural-activity relationship (QSAR) model created was statistically significant with validation metrics of R2 (0.9525), R2adj (0.9314), and CV.R (0.9719). The molecular docking analysis revealed that compound C14 demonstrated the best binding affinity towards the studied protein with binding affinity value of –10.1 kcal mol–-1 (4LRM). This is in accordance with the experimental result (IC50 = 0.69). The factors observed for ADME&T correlated well with the factors observed for the referenced drug. This study indicates that compounds C1 and C9 can be further developed as anti-epidermal growth factor receptor (EGFR) compounds. Thus, our findings may open door for the design and development of library of efficient Tetrahydroquinoline- based drug-like compounds as potential anti-LC agents.
Facile synthesis and in vitro anticancer evaluation of a new series of tetrahydroquinoline
Heliyon, 2021
Tetrahydroquinoline (THQ) is an important structure for synthesizing multiple biologically active derivatives. Thus, we developed new quinoline derivatives and investigated them as anticancer agents. First, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and other techniques were used to confirm the structure of synthesized compounds. Then, they were assessed in vitro against three human cancer cell lines. Consequently, four compounds, 10, 13, 15, and 16, were identified as promising anticancer agents with pyrazolo quinoline derivative (15) exhibiting the highest potential IC 50 and a strong apoptotic effect on three cell lines.
RSC advances, 2024
Some hexahydroquinoline candidates were prepared by reacting 2-amino-3-cyano-1cyclohexylhexahydroquinoline with oxalyl chloride and triethyl orthoformate. The computational chemical approach agreed with the product-testing results. The produced substances were examined in vitro for their antiproliferative activity against liver carcinoma (HepG2), breast adenocarcinoma (MCF7), prostate cancer (PC3), and colon cancer (HCT116) cell lines. The highest potency against the four cell lines was exhibited by hydrazide, thiosemicarbazide, and thiazolidinone derivatives. The best docking score was presented by thiosemicarbazide and thiazolidinone derivatives as they showed the highest binding to the Mcl-1 enzyme with binding energies of −8.97 and −8.90 kcal mol −1 , respectively, which were higher than that of the co-crystallized ligand (LC3) with a binding energy of −8.74 kcal mol −1. Besides, the modeling pharmacokinetics disclosed their desirable drug-likeness and oral bioavailability characteristics.
Medicine in Drug Discovery, 2019
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MOLECULAR DOCKING AND ADMET STUDY OF QUINOLINE-BASED DERIVATIVES FOR ANTI-CANCER ACTIVITY
An In silico study was carried out on a series of novel quinoline based inhibitors which were designed, synthesized and assessed for their in vitro activity versus the human colon cancer cell line HT29 and the human breast cancer cell line MDA-MB231 by Arafa RK et. al. We have designed these 22 inhibitors in ChemBioOffice 2010 and minimized using the LigPrep tool of Schrödinger 2011. Docking study of these inhibitors was performed on different cancer proteins in order to give a suggestion to the proposed in vitro mechanism of action. Some prominent cancer proteins specifically causing breast and colon cancers are used as targets in this computational study to predict the most active quinoline based derivative. The proteins are minimized using the protein preparation wizard and Grid is generated by specifying the active site amino acids. The binding model of best scoring inhibitor with each protein was assessed from their G-scores and disclosed by docking analysis using the XP visualizer tool. Interestingly the result of docking was found to match with the previous invitro study where the most active derivative against both tested cell lines was the Schiff's base 4e. The pharmacokinetic parameters study was done using the QikProp 3.4 tool to display ADME and toxicity properties of these inhibitors.
Journal of Molecular Modeling, 2019
Quinolinones and sulfonamides are moieties with biological potential that can be linked to form new hybrid compounds with improved potential. However, there are few hybrids of these molecules reported. In this sense, this work presents a structural description of a new sulfonamide-dihydroquinolinone (E)-2-(2-methoxyphenyl)-3-(3-nitrobenzylidene)-1-(phenylsulfonyl)-2,3 dihydroquinolin-4(1H)-one (DHQ). The molecular structure of DHQ was elucidated by X-ray diffraction, nuclear magnetic resonance and infrared spectroscopy, and both molecular packing and intermolecular interactions were analyzed by Hirshfeld surfaces and fingerprint maps. In addition, theoretical calculations on frontier orbitals, molecular electrostatic potential maps, and assignments were performed. The crystal packing of DHQ was found to be stabilized by a dimer through a weak C-H⋯O interaction along the c axis. Moreover, the structure is stabilized mainly by C-H⋯O and C-H⋯π interactions, since the interaction C25-H25⋯π contributes to a chain formation. The Hirshfeld normalized surface shows that the closest interactions are around the atoms linked to the dimer formation. The calculations indicate that DHQ possesses electrophilic sites near O atoms and depleted electrons around the H atoms. There is a band GAP of 3.29 eV between its frontier orbitals, which indicates that DHQ is more reactive than other analogues published.
Asian Journal of Chemistry, 2014
Cancer is a multifaceted disease that represents one of the leading causes of mortality in developed countries. Worldwide, one in eight deaths is due to cancer and it is the second most common cause of death in the US, exceeded only by heart disease 1 Chemotherapy is the mainstay for cancer treatment, the use of available chemotherapeutics is often limited due to undesirable side effects. It is important to identify new agents and new targets for the treatment of cancer. Nitrogen heterocycles have received a great deal of attention in the literature due to their role as active pharmacophores of historical significance. Among these heterocyclic systems, especially those containing pyridine rings are associated with diverse pharmacological properties such as anticancer 2,3 , antimicrobial 4-6 , anticonvulsant 7 , antiviral 8 anti-HlV 9 , antifungal and antimycobacterial activities 10. Recently considerable attention has been devoted to the construction of new derivatives of quinoline on the account of their reported biological activities 11-18. From the literature survey, several methods have been described for the elaboration of substituted quinolines 19-21 , which as a class have been reported to have anticancer and antileukemic activity. Different mechanisms account for the cytotoxic effect of this class of compounds, the most prominent mechanism was the inhibition of carbonic anhydrase isozymes Design, Synthesis, X-Ray Crystallographic Study and Anticancer Activity of Novel 4-(7-Chloro-1-methylquinolin-4-(1H)-ylideneamino)-phenyl-3-(dimethylamino)-prop-2-en-1-one
Journal of Pharmaceutical Research International
A new series of (2-(substituted-phenyl) quinoline-4-yl) (3-(substituted phenyl)-5-phenyl-1H-pyrazol-1-yl) methanone derivatives was carried out docking modelling and synthesized. Purity was checked by TLC and chemical structures of synthesized compounds were elucidated by their IR, 1HNMR, MS analysis data. The synthesized compounds were screened for anticancer activity by using cell line MCF-7 (Human breast cancer cell line) correlate with docking modelling.
Benzoquinoline Derivatives: An Attractive Approach to Newly Small Molecules with Anticancer Activity
International Journal of Molecular Sciences
This study presents the synthesis, structural characterization, and in vitro evaluation of anticancer activity of some newly benzo[f]quinoline derivatives. The synthesis is facile and efficient, involving two steps: quaternization of nitrogen heterocycle followed by a [3+2] dipolar cycloaddition reaction. The synthesized compounds were characterized by FTIR, NMR, and X-ray diffraction on monocrystal in the case of compounds 6c and 7c. An in vitro single-dose anticancer assay of eighteen benzo[f]quinoline compounds, quaternary salts, and cycloadducts, was performed. The results showed that the most active compounds were quaternary salts 3d and 3f with aromatic R substituents. Quaternary salt 3d revealed non-selective activity against all types of cancer cells, while salt 3f exhibited a highly selective activity against leukemia cells. Compound 3d also presented remarkable cytotoxic efficiency against four distinct types of cancer cells—namely, non-small cell lung cancer HOP–92, melan...