Synthesis, biological evaluation, and computational studies of novel fused six-membered O-containing heterocycles as potential acetylcholinesterase inhibitors

Pourshojaei, Yaghoub; Abiri, Ardavan; Eskandari, Razieh; Dourandish, Fatemeh; Eskandari, Khalil; Asadipour, Ali

doi:10.1016/j.compbiolchem.2019.04.004

Cited by 14 publications

(10 citation statements)

References 54 publications

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“…The particle‐mesh‐based Ewald pattern was utilized for summation of long‐range electrostatic forces. A cutoff radius range of 9.0 Å was set for computation of Columbic forces [34, 49, 50].…”

Section: Methodsmentioning

confidence: 99%

Phlorotannins as HIV Vpu inhibitors, an in silico virtual screening study of marine natural products

Langarizadeh

Abiri

Ghasemshirazi

et al. 2020

Biotech and App Biochem

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The importance of new effective treatment methodologies for human immunodeficiency virus (HIV) is undeniable for the medical society. Viral protein U (Vpu), one of the disparaged accessory proteins of HIV, is responsible for the dissemination of viral particles, and HIV mutants lacking Vpu protein have remarkably reduced pathogenicity. Here, we explored the marine natural products to find the leading structures which can potentially inhibit the activity of Vpu in silico. To fulfill this goal, we set up a virtual screening based on molecular docking to evaluate the binding capacity of different marine products to Vpu. For validation, we used molecular dynamics simulation and monitored the root mean square deviation value and binding interactions. The results were intriguing when we realized that the hit compounds (phlorotannins) had previously been identified as reverse transcriptase and HIV protease inhibitors. This research inaugurates a new road to combat HIV by multifaceted mode of action of these marine natural products without putting the normal cells in jeopardy (with their safe toxicological profile).

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Section: Methodsmentioning

confidence: 99%

Phlorotannins as HIV Vpu inhibitors, an in silico virtual screening study of marine natural products

Langarizadeh

Abiri

Ghasemshirazi

et al. 2020

Biotech and App Biochem

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“…Subsequently, compounds 30 were evaluated in silico against acetylcholinesterase enzyme (AChE) and their Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMETox) properties were also studied, to make the results more reliable and introduce them as remarkable potential candidates for inhibition of AChE, in the treatment of Alzheimer's, Parkinson's and autism diseases. Among the evaluated products, compound 30f (R = p-OCH 2 C 6 H 4 Br) showed the best activity against AChE [48].…”

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Synthesis of Biologically Active Molecules through Multicomponent Reactions

et al. 2020

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Focusing on the literature progress since 2002, the present review explores the highly significant role that multicomponent reactions (MCRs) have played as a very important tool for expedite synthesis of a vast number of organic molecules, but also, highlights the fact that many of such molecules are biologically active or at least have been submitted to any biological screen. The selected papers covered in this review must meet two mandatory requirements: (1) the reported products should be obtained via a multicomponent reaction; (2) the reported products should be biologically actives or at least tested for any biological property. Given the diversity of synthetic approaches utilized in MCRs, the highly diverse nature of the biological activities evaluated for the synthesized compounds, and considering their huge structural variability, much of the reported data are organized into concise schemes and tables to facilitate comparison, and to underscore the key points of this review.Molecules 2020, 25, 505 2 of 71 acetylcholinesterase inhibitors, anti-HIV, antimicrobial, antioxidant, anti-mycobacterial and anticancer activities ( Figure 1). It is noteworthy that 64% and 16% of the supporting literature found for this review correspond to heterocyclic structures with anticancer and antimicrobial activities, respectively. Scheme 2. Three-component synthesis of 3,4-dihydropyrimidinones/thiones type 7 under microwave irradiation, for anti-inflammatory activity.Patil et al., reported a one-pot pseudo-five-component synthesis of highly functionalized tetrahydropyridines 9 using Cu(OTf) 2 as catalyst, Scheme 3. In vitro anti-inflammatory activity of the obtained compounds 9 was determined against matrix metalloproteinases (MMPs) as MMP-2 and MMP-9 by using gelatin zymography [29]. Scheme 3. Multicomponent Cu(OTf) 2 catalyzed synthesis of substituted tetrahydropyridines 9 for anti-inflammatory activity.A highly diastereoselective synthesis (exclusively the cis isomer is formed), of chromeno β-lactam hybrids 13/14 was also achieved by an efficient one-pot three-component reaction between either 5,5-dimethylcyclohexane-1,3-dione (10a) or 4-hydroxycoumarin (10b), diverse benzaldehydes 11 and malononitrile (12), in the presence of DABCO under reflux conditions (Scheme 4). Scheme 4. Three-component synthesis of β-lactam hybrids 13/14 for anti-inflammatory activity.The synthesized compounds (13 in 80-95% yield) and (14 in 82-95% yield) were screened for anti-inflammatory activity (as well as for anticancer activity, please see Section 3.13.13. Compound 13b (Ar = 4-ClC 6 H 4 , Ar 1 = 4-MeC 6 H 4 ) was the most active of all the chromeno β-lactam hybrids 13/14 tested, with a 19.8 anti-inflammatory ratio, although, it resulted less active than the reference drug dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation [30].

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“…As search algorithms, Lamarckian Genetic Algorithm (LGA) was applied and performed by AutoDock 4.2. [17,[19][20][21]. Finally, the PDBQT file of the receptors was obtained using MGLTOOLS 1.5.6.…”

Section: Docking Proceduresmentioning

confidence: 99%

Imidazole and carbazole derivatives as potential anticancer agents: molecular docking studies and cytotoxic activity evaluation

Taheri¹,

Taghavi²,

Zarei³

et al. 2020

Bull. Chem. Soc. Eth.

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Carbazoles and imidazole represent two important classes of heterocycles which exhibit diverse biological activities such as antitumor properties. In this study, imidazole (C1-C3) and carbazole (C4 and C5) derivatives were evaluated for their cytotoxic activity against three human cancer cell lines namely, MCF7 (human breast cancer), HT29 (human colon cancer), and HeLa (human cervical cancer). Carbazole derivatives (C4 and C5) with IC50 < 10 µM showed greater cytotoxic effect than imidazole derivatives (C1-C3). Furthermore, all compounds exhibited better anticancer activity against MCF-7 than other two cell lines (HT-29, HeLa) and compound C4 was the most potent compound with the IC50 values of 2.5, 5.4 and 4.0 µM, against MCF-7, Hela and HT-29 cell lines, respectively. Physicochemical properties of compounds were calculated and their correlation with the IC50 values on MCF-7 cell line investigated. Surface area and polarizability of compounds showed good correlation by R2 = 0.8396 and R2 = 0.834, respectively. Docking studies of these compounds were also performed on the DNA as proposed target to comprehend their binding interactions and binding energies. The docking energy of compounds ranged from - 11.32 to -13.48 kcal/mol. Compound C3 with energy of -13.48 kcal/mol had the highest docking energy. Docking results indicated that these compounds (C1-C5) had strong affinity in binding to the DNA. KEY WORDS: Imidazole, Carbazole, Molecular docking, Cancer, MTT assay Bull. Chem. Soc. Ethiop. 2020, 34(2), 377-384 DOI: https://dx.doi.org/10.4314/bcse.v34i2.14

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Synthesis, biological evaluation, and computational studies of novel fused six-membered O-containing heterocycles as potential acetylcholinesterase inhibitors

Cited by 14 publications

References 54 publications

Phlorotannins as HIV Vpu inhibitors, an in silico virtual screening study of marine natural products

Phlorotannins as HIV Vpu inhibitors, an in silico virtual screening study of marine natural products

Synthesis of Biologically Active Molecules through Multicomponent Reactions

Imidazole and carbazole derivatives as potential anticancer agents: molecular docking studies and cytotoxic activity evaluation

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