<i>In Vitro</i> Evaluation of the Multidrug Resistance Reversing Activity of Novel Imidazo[4,5-b]pyridine Derivatives

Bourichi, S.; Misbahi, Houria; Rodi, Youssef Kandri; Chahdi, Fouad Ouazzani; Essassi, El Mokhtar; Szabo, S. M.; Szalontai, Beatrix; Gajdács, Márió; Molnár, Joséph; Spengler, Gabriella

doi:10.21873/anticanres.12687

Cited by 10 publications

(6 citation statements)

References 16 publications

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“…Among the derivatives of 2,3-diaminopyridine, 5-bromo-2,3-diaminopyridine appears as a potentially important synthon involved in the synthesis of imidazo[4,5-b]pyridine [ 27 ]. Indeed, the condensation of this compound with the benzaldehyde led to the formation of the expected imidazo[4,5-b]pyridine derivative ( 1 ) ( Scheme 1 ).…”

Section: Resultsmentioning

confidence: 99%

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study

et al. 2023

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5-bromopyridine-2,3-diamine reacted with benzaldehyde to afford the corresponding 6-Bromo-2-phenyl-3H-imidazo[4,5-b]pyridine (1). The reaction of the latter compound (1) with a series of halogenated derivatives under conditions of phase transfer catalysis solid–liquid (CTP) allows the isolation of the expected regioisomers compounds (2–8). The alkylation reaction of (1) gives, each time, two regioisomers, N3 and N4; in the case of ethyl bromoactate, the reaction gives, at the same time, the three N1, N3 and N4 regioisomers. The structures of synthesized compounds were elucidated on the basis of different spectral data (1H NMR, 13C NMR), X-Ray diffraction and theoretical study using the DFT method, and confirmed for each compound. Hirshfeld surface analysis was used to determine the intermolecular interactions responsible for the stabilization of the molecule. Density functional theory was used to optimize the compounds, and the HOMO-LUMO energy gap was calculated, which was used to examine the inter/intra molecular charge transfer. The molecular electrostatic potential map was calculated to investigate the reactive sites that were present in the molecule. In order to determine the potential mode of interactions with DHFR active sites, the three N1, N3 and N4 regioisomers were further subjected to molecular docking study. The results confirmed that these analogs adopted numerous important interactions, with the amino acid of the enzyme being targeted. Thus, the most docking efficient molecules, 2 and 4, were tested in vitro for their antibacterial activity against Gram-positive bacteria (Bacillus cereus) and Gram-negative bacteria (Escherichia coli). Gram-positive bacteria were more sensitive to the action of these compounds compared to the Gram-negative, which were much more resistant.

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Section: Resultsmentioning

confidence: 99%

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study

et al. 2023

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“…Then, the medium was removed and the cells were incubated with the various compounds at 37˚C for 24 h. At the end of the incubation period, 20 μl of MTT solution (from a stock solution of 5 mg/mL) were added to each well. After incubation at 37˚C for 4 h, 100 μl of sodium dodecyl sulfate (SDS) (Sigma) solution (10% in 0.01 M HCI) were added to each well and the plates were further incubated at 37˚C overnight (14,15,18). Cell growth was determined by measuring the optical density (OD) at 540/630 nm with Multiscan ANTICANCER RESEARCH 40: xxx-xxx (2020) EX ELISA reader (Thermo Labsystems, Cheshire, WA, USA).…”

Section: Methodsmentioning

confidence: 99%

Phenothiazines and Selenocompounds: A Potential Novel Combination Therapy of Multidrug Resistant Cancer

et al. 2020

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Background/Aim: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. Materials and Methods: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay. Results: Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 μM). Thioridazine was the most potent among the three phenothiazines. Conclusion: Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, therefore, their use as adjuvants in cancer may be considered as a potential drug repurposing strategy.

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“…The family of nitrogenous drugs, particularly those containing the imidazopyridine moiety, is important in medicinal chemistry because of their wide range of pharmacological activities such as anticancer, anti-inflammatory, antibacterial, antituberculosis, anti-glycation anti-analgesic and antifungal properties, and their antioxidant potential. In particular, imadazo [4,5-b]pyridine derivatives inhibit the P-glycoprotein, which could reverse the multidrug resistance of cancer cells (Bourichi et al, 2018). They are also inhibitors of type 2 diabetes because of their ability to inhibit the Baker's yeastglucosidase enzyme, and are inhibitors of one or more proteins in the treatment of disorders characterized by the activation of Wnt pathway signalling (for example: cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases and osteoarthritis), and of genetic and neurological diseases such as PAK4 kinase 4 inhibitor activated by p21 and aurora kinase inhibitors.…”

Section: Chemical Contextmentioning

confidence: 99%

Crystal structure, Hirshfeld surface analysis and DFT study of 6-bromo-3-(5-bromohexyl)-2-[4-(dimethylamino)phenyl]-3H-imidazo[4,5-b]pyridine

et al. 2020

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In the title molecule, C20H24Br2N4, the imidazopyridine moiety is not planar as indicated by the dihedral angle of 2.0 (2)° between the constituent rings; the 4-dimethylaminophenyl ring is inclined to the mean plane of the imidazole ring by 27.4 (1)°. In the crystal, two sets of C—H...π(ring) interactions form stacks of molecules extending parallel to the a-axis direction. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H (42.2%), H...C/C...H (23.1%) and H...Br/Br...H (22.3%) interactions. The optimized structure calculated using density functional theory (DFT) at the B3LYP/ 6–311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated HOMO–LUMO energy gap is 2.3591 eV.

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In Vitro Evaluation of the Multidrug Resistance Reversing Activity of Novel Imidazo[4,5-b]pyridine Derivatives

Abstract: Based on our experimental results, compounds that showed potent activity are those with a short carbon side chain; a methoxy group on the benzene ring; a heterocyclic (triazole) side chain and the presence of an alkylated N-atom at position 4.

Cited by 10 publications

References 16 publications

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study

Phenothiazines and Selenocompounds: A Potential Novel Combination Therapy of Multidrug Resistant Cancer

Crystal structure, Hirshfeld surface analysis and DFT study of 6-bromo-3-(5-bromohexyl)-2-[4-(dimethylamino)phenyl]-3H-imidazo[4,5-b]pyridine

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