A promising anti-cancer and anti-oxidant agents based on the pyrrole and fused pyrrole: synthesis, docking studies and biological evaluation (original) (raw)
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A series of N-aryl derivatives of pyrrole and its related derivatives of fused form (namely; tetrahydroindole and dihydroindenopyrroles) were prepared in fair to good yields. The newly synthesized compounds were confirmed using IR, 1 H NMR, Mass spectral and elemental analysis. Tetrahydrobenzo [b] pyrroles Ia-d, 1,4-dihydroindeno[1,2-b]pyrroles IIa,b and pyrroles IIIa-c,e were evaluated for anticancer activity, coinciding with the antioxidant activity; using Di-Phenyl Picryl Hydrazyl (DPPH) tests. The cytotoxicity of the tested compounds (at a concentration of 100 and 200 µg /mL) was performed against HepG-2 and EACC cell lines. Compounds Ib, d and IIa showed promising antioxidant activity beside their anticancer activity. Docking studies were employed to justify the promising anticancer activity of Ib,d and IIa. Protein kinase (PKase)-PDB entry 1FCQ was chosen as target enzyme for this purpose using the MOLSOFT ICM 3.4-8C program. The docking results of the tested compounds went aligned with the respective anticancer assay results. Silica gel 60 (particle size 0.06-0.20 mm). Compound Ia prepared by the mentioned procedure had the same m.p. as reported by and III a-c were prepared as reported in the literature. All new compounds yielded spectral data consistent with the proposed structure and microanalysis within ±0.4% of the theoretical values.
International Journal of Molecular Sciences
The current study describes the synthesis, physicochemical characterization and cytotoxicity evaluation of a new series of pyrrole derivatives in order to identify new bioactive molecules. The new pyrroles were obtained by reaction of benzimidazolium bromide derivatives with asymmetrical acetylenes in 1,2-epoxybutane under reflux through the Huisgen [3 + 2] cycloaddition of several ylide intermediates to the corresponding dipolarophiles. The intermediates salts were obtained from corresponding benzimidazole with bromoacetonitrile. The structures of the newly synthesized compounds were confirmed by elemental analysis, spectral techniques (i.e., IR, 1H-NMR and 13C-NMR) and single-crystal X-ray analysis. The cytotoxicity of the synthesized compounds was evaluated on plant cells (i.e., Triticum aestivum L.) and animal cells using aquatic crustaceans (i.e., Artemia franciscana Kellogg and Daphnia magna Straus). The potential antitumor activity of several of the pyrrole derivatives was st...
Pyrrole derivatives as potential anti-cancer therapeutics: synthesis, mechanisms of action, safety
Journal of Drug Targeting, 2019
Pyrrole derivatives (PDs) chloro-1-(4-chlorobenzyl)-4-((3-(trifluoromethyl)phenyl)amino)-1H-pyrrole-2,5-dione (MI-1) and 5-amino-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2dihydro-3H-pyrrole-3-one (D1) were synthesized as inhibitors of several protein kinases including EGFR and VEGFR. The aim of the study was to reveal the exact mechanisms of PDs' action EGFR and VEGFR are involved in. We observed, that both PDs could bind with EGFR and VEGFR and form stable complexes. PDs entered into electrostatic interactions with polar groups of phospholipid heads in cell membrane, and the power of interaction depended on the nature of PD radical substituents (greater for MI-1 and smaller for D1). Partial intercalation of MI-1 into the membrane hydrophobic zone also occurred. PDs concentrations induced apoptosis in malignant cells but normal ones had different sensitivity to those. MI-1 and D1 acted like antioxidants in inflamed colonic tissue, as evidenced by reduce of lipid and protein peroxidation products (by 43-67%) and increase of superoxide dismutase activity (by 40 and 58%) with restoring these values to control ones. MI-1 restored reduced hemoglobin and normalized elevated platelets and monocytes in settings of colorectal cancer, whereas D1 normalized only platelets. Thus, MI-1 and D1 could be used as competitive inhibitors of EGFR and VEGFR and antioxidants, which might contribute to realization of their anti-inflammatory, proapoptotic and antitumor activity.
Synthesis of new pyrrole and pyrrolo[2,3-d]pyrimidine derivatives of potential antioxidant activity
ChemPlusChem, 2010
New 2-amino-3-cyanopyrrole derivatives were prepared and converted to 7-deazapurines. 7-Deazaadenine 6 was synthesized by different methods and alkylated with alkyl iodides to afford the quaternized 3-alkylpyrrolopyrimidinium iodide salts 8. The latter salts were dequaternized to N-alkylpyrrolo[2,3-d]pyrimidin-4-amines 12. Compounds 12 were identical to the products obtained from reactions of 4-chloro-7-(4-fluorophenyl)-5-p-tolyl-7H-pyrrolo-[2,3-d]pyrimidine 11 with methyl-or ethylamine in the presence of a catalyst. The thione 13 and its related 4-methylthio-and 4-ylcarbonothioate derivatives 14a, 14b were obtained. The triazolo-17a-17e, benzenesulfonamido-19, and tetrazolopyrrolopyrimidine 21 derivatives were synthesized. Several examples of the synthesized pyrrole-and pyrrolo[2,3-d]pyrimidine derivatives showed high to remarkable antioxidant scavenging activity as measured by their ability to scavenge the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical
Synthesis, characterization and biological activity of novel pyrrole compounds
5-((1, 3-dioxoisoindolin-2-yl) methyl-2-hydroxybenzohydrazide (1) undergoes facile condensation with aromatic aldehydes to afford the corresponding N'-Substitutedphenyl-5-((1, 3-dioxoisoindolin-2-yl) methyl)-2-hydroxy benzo hydrazides (2a-h) in good yield. Cyclocondensation of compounds (2a-h) with maleic anhydride yields 1-(5-((1, 3dioxoisoindolin-2-yl) methyl)-2-hydroxybenzamido) -5-oxo-2-substituted phenyl-2, 5-dihydro-1H-pyrrole-3carboxylic acid (3a-h). The structures of these compounds were established on the basis of analytical and spectral data. All the newly synthesized compounds were evaluated for their antibacterial and antifungal activities.
Recent synthetic and medicinal perspectives of pyrroles: An overview
2017
Pyrrole is a privileged scaffold with assorted nature of biological activities. Many active compounds have been developed by amalgamation of different pharmacophores in a pyrrole ring system. Pyrroles are an active component of complex macrocycles, including the porphyrins of heme, chlorins, bacteriochlorins, chlorophyll, porphyrinogens. Pyrrole and its derivatives are widely used as intermediates in synthesis of pharmaceuticals, agrochemicals, dyes, photographic chemicals, perfumes and other organic compounds. The pyrrole skeleton is an imperative structural framework found in extensive range of biologically active natural products and pharmaceutically active molecules. They are an element of polymers, indigoid dyes and large aromatic rings. Pyrroles are utilized as a catalyst for polymerization process, corrosion inhibitor, preservative, solvent for resins and terpenes. It is functional in various metallurgical process, luminescence chemistry, spectrochemical analysis and transiti...
Research Square (Research Square), 2022
A series of novel 2-bromo-6-(4,5-diphenyl-1-((subtituted-phenyl-1H-1,2,3-triazol-4-yl)methyl)-1H-imidazol-2yl)pyridine (7a-l) were synthesized and characterized by various analytical techniques. All the synthesized compounds were evaluated for their in vitro anticancer activity against two human cancer cell lines such as HT-1080 (Human bro sarcoma cells) and Caco-2(Human colorectal adenocarcinoma cells) and IC 50 values were compared against standard anticancer drug doxorubicin. Among all the synthesized compounds 7b, 7c and 7f has shown potent activity against HT-1080. Similarly compounds 7b and 7c shown signi cant activity among all the synthesized compounds against Caco-2. Furthermore, the results were supported by molecular docking studies.
Survey in Pyrrole Compounds and Biological Activity
Many organic compounds, including natural products, polymers, ligands and drugs. Forming a carbon−carbon bond in biaryl groups is of topical interest in synthetic organic chemistry pharmaceutical chemistry are disciplines at the intersection of chemistry, especially synthetic organic chemistry, and pharmacology and various other biological specialties, where they are involved with design, chemical synthesis and development for market of pharmaceutical agents, or bio-active molecules (drugs).Very important part of above is the heterocyclic-chemistry. Now a days so many investigation are carried out for developing new chemical entities having suitability for human life. A lot of research work is going on presently for development of new heterocyclic derivatives.The present review article is concern with the five-membered heterocyclic compound pyrrole
Journal of the Mexican Chemical Society, 2018
Based in a general structural pharmacophore model of suberoylanilide hydroxamic acid (commercially known as Vorinostat©), we synthesized a series of new pyrrolo[3,4-c]pyrrole hydroxamic acid derivatives, 9a-c, to be tested as candidates for anti-cancer drugs. The evaluation of their possible biological activity was assessed in two ways: a) computational characterization from molecular calculations and quantum reactivity descriptors and b) biological assays. Molecular docking and density functional theory calculations were performed to assess the binding properties of our newly synthesized pyrrolo[3,4-c] pyrrole hydroxamic acid derivatives, employing as the biological target the histone deacetylase isoforms available in the protein data bank. Furthermore, to characterize the effect of changing the functional groups that we varied while designing our drug model, and to improve the assessment of the binding energy, conceptual density functional theory reactivity descriptors were calculated to rationalize the capability of the new drugs to interact with the histones active site. Our findings show that the newly synthesized derivative, 9c, display the best energetic coupling with the biological target and the more favorable values of the density functional theory descriptors to interact with the active site. The biological assay of the anti-cancer drug candidates was done using three different techniques: i) anti-proliferative activity on two breast cancer cell lines; ii) Histone H3 acetylation; and iii) DNA damage. Docking studies were performed on histone deacetylase enzymes. The biological function of these enzymes is the deacetylation of histones. We analyze the level of histone acetylation in two cell lines. The computational findings are in good agreement with the biological evaluation. Our main contribution is that one of our newly synthesized derivatives, 9c, performs better than the commercial reference suberoylanilide hydroxamic acid.