First in class (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs as selective CB2 modulators targeting neurodegenerative disorders

Mingle, David; Ospanov, Meirambek; Radwan, Mohamed O.; Ashpole, Nicole M.; Otsuka, Masami; Ross, Samir A.; Walker, Larry; Shilabin, Abbas Gholipour; Ibrahim, Mohamed A.

doi:10.1007/s00044-020-02640-2

Cited by 11 publications

(12 citation statements)

References 29 publications

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“…Using the MOE build suite, the chemical structures were drawn and energy-minimized using the MOE default force field. 46 All other docking parameters were kept at their default values. Fifteen docking positions for CIPQ1 were generated.…”

Section: Methodsmentioning

confidence: 99%

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In Vitro and In Silico Study to Assess Toxic Mechanisms of Hybrid Molecules of Quinone-Benzocaine as Plastoquinone Analogues in Breast Cancer Cells

et al. 2022

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We managed to obtain three different series of 2,3-dimethyl-1,4-benzoquinones, named nonhalogenated and halogenated (brominated and chlorinated) PQ analogues, via the molecular hybridization strategy. Sixteen of eighteen hybrid molecules were selected by the National Cancer Institute (NCI) of Bethesda for their in vitro antiproliferative potential against the full NCI 60 cell line panel. The hybrid molecules ( BrPQ5 , CIPQ1 , and CIPQ3 ) showed good growth inhibition at 10 μM concentration, particularly against breast cancer cell lines. As per the results obtained from in vitro antiproliferative evaluation, cytotoxic activities of the hybrid molecules ( BrPQ5 , CIPQ1 , and CIPQ3 ) were evaluated with an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in T47D and MCF7 breast cancer and human umbilical vein endothelial (HUVEC) cells. Molecules exhibited cytotoxic activity, and especially, CIPQ1 showed remarkable cytotoxic activity and good selectivity on T47D and MCF7 cells. Furthermore, CIPQ1 could inhibit cell proliferation, cause apoptotic cell death and disturb the cell cycle in T47D and MCF7 cells. Additionally, CIPQ1 caused oxidative stress induction in both cells, more so in T47D. In vitro study results indicated that the anticancer activity of CIPQ1 was more prominent in T47D cells than in MCF7 cells. The compound CIPQ1 showed a prominent binding with JNK3 in silico . Thus, the obtained hybrid molecules via the molecular hybridization strategy of two important pharmacophores could be useful in the discovery of novel antiproliferative agents, and CIPQ1 could be considered a promising drug candidate.

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Section: Methodsmentioning

confidence: 99%

“…The cocrystallized ligand III was defined as the center of the binding site. Using the MOE build suite, the chemical structures were drawn and energy-minimized using the MOE default force field . All other docking parameters were kept at their default values.…”

Section: Methodsmentioning

confidence: 99%

In Vitro and In Silico Study to Assess Toxic Mechanisms of Hybrid Molecules of Quinone-Benzocaine as Plastoquinone Analogues in Breast Cancer Cells

et al. 2022

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“…Using the MOE build suite, the chemical structures were drawn, and then energy-minimized using the MOE default force field. 71 All other docking options were kept at their default values. Fifteen docking positions were generated for each ligand.…”

Section: Methodsmentioning

confidence: 99%

Natural-product-inspired design and synthesis of thiolated coenzyme Q analogs as promising agents against Gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking

et al. 2022

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“…The co-crystallized ligand TK-666 was defined as the center of the binding site. Using the MOE build suite, the chemical structures were drawn, and then energy-minimized using the MOE default force field [ 81 ]. All other docking options were kept at their default values.…”

Section: Methodsmentioning

confidence: 99%

Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking

et al. 2022

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In the present study, we designed and synthesized thiolated VK3 analogs (VK3a–g) along with an extensive antimicrobial study. After the evaluation of the antibacterial and antifungal activity against various bacterial and fungal strains, we presented an initial structure–activity relationship study on these VK3 analogs. In particular, four thiolated VK3 analogs exhibited superior biological potency against some Gram-positive bacterial strains, including Staphylococcus aureus (ATCC® 29213) and Enterococcus faecalis (ATCC® 29212). Next, all thiolated VK3 analogs were evaluated for their potential of cell growth inhibition on the NCI-60 cancer cell lines panel. This screening underlined that the thiolated VK3 analogs have no visible cytotoxicity on different cancer cell lines. The selected two thiolated VK3 analogs (VK3a and VK3b), having minimal hemolytic activity, which also have the lowest MIC values on S. aureus and E. faecalis, were further evaluated for their inhibition capacities on biofilm formation after evaluating their potential in vitro antimicrobial activity against each of the 20 clinically obtained resistant strains of Staphylococcus aureus. VK3b showed excellent antimicrobial activity against clinically resistant S. aureus isolates. Furthermore, the tested molecules showed nearly two log10 reduction in the viable cell count at six hours according to the time kill curve studies. Although these molecules decreased biofilm attachment about 50%, when sub-MIC concentrations were used these molecules increased the percentage of biofilm formation. The molecular docking of VK3a and VK3b in S. aureus thymidylate kinase was conducted in order to predict their molecular interactions. VK3a and VK3b exhibited excellent lead-likeness properties and pharmacokinetic profiles that qualify them for further optimization and development. In conclusion, since investigating efficient novel antimicrobial molecules is quite difficult, these studies are of high importance, especially in the present era of antimicrobial resistance.

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First in class (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs as selective CB2 modulators targeting neurodegenerative disorders

Cited by 11 publications

References 29 publications

In Vitro and In Silico Study to Assess Toxic Mechanisms of Hybrid Molecules of Quinone-Benzocaine as Plastoquinone Analogues in Breast Cancer Cells

In Vitro and In Silico Study to Assess Toxic Mechanisms of Hybrid Molecules of Quinone-Benzocaine as Plastoquinone Analogues in Breast Cancer Cells

Natural-product-inspired design and synthesis of thiolated coenzyme Q analogs as promising agents against Gram-positive bacterial strains: insights into structure–activity relationship, activity profile, mode of action, and molecular docking

Promising Antibacterial and Antifungal Agents Based on Thiolated Vitamin K3 Analogs: Synthesis, Bioevaluation, Molecular Docking

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