Design, synthesis and anticancer activity of new monastrol analogues bearing 1,3,4-oxadiazole moiety

Ragab, F. M.; Abou‐Seri, Sahar M.; Abdel‐Aziz, Salah A.; Alfayomy, Abdallah M.; Aboelmagd, Mohamed

doi:10.1016/j.ejmech.2017.06.026

Cited by 60 publications

(34 citation statements)

References 30 publications

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“…In order to better rationalize SAR of the proposed monastrol’s analogs and gain insights into the binding mode of molecules within the motor domain of Eg5, molecular docking studies were conducted. Among available X- ray structures of the Eg5-monastrol complex, the structure (PDB ID: 1Q0B) with a high resolution (1.9 Å) was chosen ( 6 27 28 29 ). The accuracy of the docking protocol was validated by removing the co-crystallized monastrol from the binding site of Eg5 and redocking into the active site.…”

Section: Discussionmentioning

confidence: 99%

Monastrol derivatives: in silico and in vitro cytotoxicity assessments

et al. 2020

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Background and purpose: Cancer is the leading cause of death in today’s world, therefore the efforts to achieve anticancer drugs with higher potency and fewer side effects have always been conducted by researchers in the field of pharmaceutical chemistry. Monastrol, a cytotoxic small molecule, from dihydropyrimidinone scaffold, is an inhibitor of the kinesin-5 protein. So, efforts to identify more derivatives of this molecule have been of interest. Experimental approach: Some of monastrol’s analogs as Eg5 inhibitors with different substitution patterns were analyzed, synthesized, and their cytotoxic effects were evaluated on MCF-7 and HeLa cancerous cells in vitro using the MTT assay. The structure-activity relationship (SAR) was studied in silico by molecular docking. Findings / Results: Among all proposed structures, in ducking study, those with hydrophobic moieties on the C2-N3 region, those with a hydroxyl group on the phenyl on C4 position, and those with a carboxylic group on C5 were the best candidates. In vitro studies, on the other side, emphasized that monastrol still was the most potent derivative. Another finding was the more moderate activity of synthesized compounds on the HeLa cell compared to the MCF-7 cell line. During different challenges for substitution at 5-position, some earlier reports around the dihydropyrimidinone reactions were questioned. It seems that the change at the position 5 is not merely accessible, as earlier reports claimed. Also, we could not achieve any better cell cytotoxicity by the larger group in the thiourea region or position 5; nonetheless, it seems that the introduction of a methylene group at this position could be beneficial. Conclusion and implications: The initial results of this study were valuable in terms of design and synthesis and will be useful for future investigations.

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Section: Discussionmentioning

confidence: 99%

Monastrol derivatives: in silico and in vitro cytotoxicity assessments

et al. 2020

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“…54 In DOCA-salt and L-NNA hypertensive rats, the mean systolic blood pressure was 185.3±4.7 and 170.2±4.1 mmHg, whereas after administration of NOX-1 to hypertensive rats, MSBB was 127.8±4.5 and 120.2±5.1mmHg, respectively. 51 The prepared derivatives were evaluated for their cytotoxic activity against 60 cancer cell lines at one dose (10 μM). Compounds 54 against HL-60 (TB) and 55 ( Figure 49) against MOLT-4, were found to be more active than monastrol.…”

Section: Calcium Channel Blockermentioning

confidence: 99%

Recent Developments on Pharmacological Potential of 1,3,4-Oxadiazole Scaffold

Bhutani¹,

P²,

Kapoor³

et al. 2019

IJPER

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“…Fatma et al [56] reported the synthesis, characterization and anticancer activity of new monastrol analogues bearing 1,3,4-oxadiazole moiety. In the synthesized series 9i, 9k, 9m and 9n possessed significant activity against HL-60(TB) and MOLT-4 compared to monastrol.…”

Section: Synthesis Of Dihydropyrimidine (Dhpm) Derivatives Bearing 1mentioning

confidence: 99%

A Review on the Preparation of 1,3,4-Oxadiazoles From the Dehydration of Hydrazines and Study of Their Biological Roles

Nayak

Poojary

2019

Chemistry Africa

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Heterocyclic chemistry is the interesting area for the effective approach and for the invention of biologically active 1,3,4-oxadiazole cores. 1,3,4-Oxadiazole is a five membered heterocyclic ring which plays key role in the development of new medicinal species for the treatment of numerous diseases. Hence, nowadays researchers have developed the innovative methods for the synthesis of 1,3,4-oxadiazole derivatives and their medicinal applications. Therefore, results of recent developments in the synthesis and biological applications of 1,3,4-oxadiazole candidates over the past 15 years (2005-2019) are reviewed in the present article. The information in the present article may be useful to many researchers which lead to exploration of new therapeutic species for the society.

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Design, synthesis and anticancer activity of new monastrol analogues bearing 1,3,4-oxadiazole moiety

Cited by 60 publications

References 30 publications

Monastrol derivatives: in silico and in vitro cytotoxicity assessments

Monastrol derivatives: in silico and in vitro cytotoxicity assessments

Recent Developments on Pharmacological Potential of 1,3,4-Oxadiazole Scaffold

A Review on the Preparation of 1,3,4-Oxadiazoles From the Dehydration of Hydrazines and Study of Their Biological Roles

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