5-Chlorobenzofuran-2-carboxamides: From allosteric CB1 modulators to potential apoptotic antitumor agents

Youssif, Bahaa G.M.; Mohamed, Ashraf M.; Osman, Essam Eldin A.; Abou-Ghadir, Ola F.; Elnaggar, Dina H.; Abdelrahman, Mostafa H.; Treamblu, Laurent; Gomaa, Hesham A.M.

doi:10.1016/j.ejmech.2019.05.040

Cited by 52 publications

(41 citation statements)

References 45 publications

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“…A human mammary gland epithelial cell line (MCF-10A) was used to conduct a cell viability assay [ 38 ]. Compounds 2–6 were incubated with MCF-10A cells for four days, and the viability of the cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

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Design, Synthesis, and Antibacterial Screening of Some Novel Heteroaryl-Based Ciprofloxacin Derivatives as DNA Gyrase and Topoisomerase IV Inhibitors

et al. 2021

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A novel series of ciprofloxacin hybrids comprising various heterocycle derivatives has been synthesized and structurally elucidated using 1H NMR, 13C NMR, and elementary analyses. Using ciprofloxacin as a reference, compounds 1–21 were screened in vitro against Gram-positive bacterial strains such as Staphylococcus aureus and Bacillus subtilis and Gram-negative strains such as Escherichia coli and Pseudomonas aeruginosa. As a result, many of the compounds examined had antibacterial activity equivalent to ciprofloxacin against test bacteria. Compounds 2–6, oxadiazole derivatives, were found to have antibacterial activity that was 88 to 120% that of ciprofloxacin against Gram-positive and Gram-negative bacteria. The findings showed that none of the compounds tested had antifungal activity against Aspergillus flavus, but did have poor activity against Candida albicans, ranging from 23% to 33% of fluconazole, with compound 3 being the most active (33% of fluconazole). The most potent compounds, 3, 4, 5, and 6, displayed an IC50 of 86, 42, 92, and 180 nM against E. coli DNA gyrase, respectively (novobiocin, IC50 = 170 nM). Compounds 4, 5, and 6 showed IC50 values (1.47, 6.80, and 8.92 µM, respectively) against E. coli topo IV in comparison to novobiocin (IC50 = 11 µM).

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Section: Resultsmentioning

confidence: 99%

“…MTT Assay was performed to investigate the effect of compounds 2–6 on the viability of mammary epithelial cells (MCF-10A) [ 38 , 39 ] (see Appendix A ).…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Antibacterial Screening of Some Novel Heteroaryl-Based Ciprofloxacin Derivatives as DNA Gyrase and Topoisomerase IV Inhibitors

et al. 2021

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“…For instance, CB2 agonist, LV50 elicited cytotoxic effect in lymphoblastoid cells with high specificity to neoplasm cells [268], and WIN 55,212-2, CB1/2 agonist was able to arrest cell cycle and cause apoptosis in renal carcinoma in vitro [269]. In addition, allosteric CB1 modulators inhibiting cell proliferation in vitro [270] are a promising approach. Such compounds may allow for avoiding CB1 activation-related adverse effects.…”

Section: Cancermentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.

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“…The antiproliferative activity of 5b , 5d , 5e , 5g , 5j and 5n against four human cancer cell lines including pancreatic cancer cell line (Panc-1), breast cancer cell line (MCF-7), colon cancer cell line (HT-29) and epithelial cancer cell line (A-549) using MTT assay and doxorubicin was applied as the reference compound [ 22 , 23 ]. Graph Pad Prism software (Graph Pad Software, San Diego, CA, USA) was used to calculate the median inhibition concentration (IC 50 ) and results are recorded in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors

et al. 2021

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A novel series of tri-aryl imidazole derivatives 5a–n carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA IX and XII activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of 5g > 5b > 5d > 5e > 5g > 5n (Ki = 0.3–1.3 μM, and selectivity ratio for hCA IX over hCA XII = 5–12) relative to acetazolamide (Ki = 0.03 μM, and selectivity ratio for hCA IX over hCA XII = 0.20). The previous sixth inhibitors have been further investigated for their anti-proliferative activity against four different cancer cell lines using MTT assay. Compounds 5g and 5b demonstrated higher antiproliferative activity than other tested compounds (with GI50 = 2.3 and 2.8 M, respectively) in comparison to doxorubicin (GI50 = 1.1 M). Docking studies of these two compounds adopted orientation and binding interactions with a higher liability to enter the active side pocket CA-IX selectively similar to that of ligand 9FK. Molecular modelling simulation showed good agreement with the acquired biological evaluation.

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5-Chlorobenzofuran-2-carboxamides: From allosteric CB1 modulators to potential apoptotic antitumor agents

Cited by 52 publications

References 45 publications

Design, Synthesis, and Antibacterial Screening of Some Novel Heteroaryl-Based Ciprofloxacin Derivatives as DNA Gyrase and Topoisomerase IV Inhibitors

Design, Synthesis, and Antibacterial Screening of Some Novel Heteroaryl-Based Ciprofloxacin Derivatives as DNA Gyrase and Topoisomerase IV Inhibitors

A Guide to Targeting the Endocannabinoid System in Drug Design

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors

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