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- Title
In Silico Studies of New Telomerase Inhibitors.
- Authors
Abdel-Aziz, Naglaa I.; Abou-Zeid, Laila A.; Mohamed, Mohamed A.-E.; Abd-Elmonaem, Ahmed S.; Elbatal, Hamdi A.; Helmy, Mohamed H.; Abd-Elhady, Abd-Elhady M.; Ali, Medhat E.; Kishk, Abd-Elrahman M.; Hegazy, Ahmed M.; Elmahdy, Mohamed A.; Elemam, Mohamed N.
- Abstract
Many studies have demonstrated that treatment with NSAIDs reduces the incidence and mortality of a wide range of tumors. The anticarcinogenic effects of NSAIDs are primarily attributed to their COX-2 inhibitory activity. However, increasing evidence suggests the involvement of molecular targets other than COX in the anti-proliferative effects and induction of apoptosis of selective COX-2 inhibitors such as telomerase enzyme. Telomerase has been found to be activated in more than 80% of human cancers and, therefore, can be considered as a potential marker for tumorigenesis. In this work, the drug-likeness of 14 reported 5,5-diphenylimidazolidine-2,4-diones, as potential COX-2 inhibitors, was calculated using Molsoft program and 10 of the tested compounds showed acceptable drug-likeness scores. Compound 3 which showed good COX-2 inhibitory activity is not expected to show acceptable pharmacokinetic profile according to the low drug-likeness score obtained (-0.11). However, the less potent compounds 10 and 13 showed the best drug-likeness scores 0.70 and 0.86, respectively. Docking of compound 13 into telomerase enzyme active site, showed three strong hydrogen bonds with the conserved aminoacids (LYS 406, & LYS 189 and ASP 343) and hence, can provide proper telomerase inhibition and consequently promising antitumor activity.
- Subjects
TELOMERASE; ANTINEOPLASTIC agents; MOLECULAR docking; HYDROGEN bonding; APOPTOSIS
- Publication
Delta University Scientific Journal, 2022, Vol 5, Issue 1, p30
- ISSN
2636-3046
- Publication type
Article
- DOI
10.21608/dusj.2022.233892