Tools
Tools
Tammam, Mohamed A., Gamal El-Din, Mariam I., Aouidate, Adnane and El-Demerdash, Amr 
ORCID: https://orcid.org/0000-0001-6459-2955
(2024)
Cephalostatins and ritterazines: Distinctive dimeric marine-derived steroidal pyrazine alkaloids with intriguing anticancer activities.
Bioorganic Chemistry, 151.
ISSN 0045-2068
Abstract
Cephalostatins and ritterazines represent fascinating classes of dimeric marine derived steroidal alkaloids with unique chemical structures and promising biological activities. Originally isolated from marine tube worms and the tunicate Ritterella tokioka collected off the coast of Japan, cephalostatins and ritterazines display potent anticancer effects by inducing apoptosis, disrupting cell cycle progression, and targeting multiple molecular pathways. This review covers the chemistry and bioactivities of 45 cephalostatins and ritterazines from 1988 to 2024, highlighting their complex structures and medicinal contributions. With insights into their structure activity relationships (SAR). Key structural elements, such as the pyrazine ring and 5/6 spiroketal moieties, are found crucial for their biological effects, suggesting interactions with lipid membranes or hydrophobic protein domains. Additionally, the formation of oxocarbenium ions from spiroketal cleavage may enhance their potency by covalently modifying DNA. The pharmacokinetics, ADMET and Drug likeness properties of these steroidal alkaloids are thoroughly addressed. Drug likeness analysis shows that these compounds fit well with the Rule of 4 (Ro4) for Protein-Protein Interaction Drugs (PPIDs), underscoring their potential in this area. Ten compounds (20, 27, 33, 34, 39, 40, 41, 42, 43, and 45) have demonstrated favourable pharmacokinetic and ADMET profiles, making them promising candidates for further research. Future efforts should focus on alternative administration routes, structural modifications, and innovative delivery systems, such as prodrugs and nanoparticles, to improve bioavailability and therapeutic effects. Advances in synthetic chemistry, mechanistic insights, and interdisciplinary collaborations will be essential for translating cephalostatins and ritterazines into effective anticancer therapies.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: Amr El-Demerdash is immensely grateful to the John Innes Centre, Norwich Research Park (UK) for the postdoctoral fellowship. Prof. Anne Osbourn is gratefully acknowledged. Mohamed A. Tammam is humbly dedicating this work to the soul of his sister Dr. Mai A. Tammam who passed away on 19 March 2022, was always a kind. supporter in all aspects of his life. Publisher Copyright: © 2024 Elsevier Inc. |
| Uncontrolled Keywords: | anticancer,cephalostatins,marine natural products,pharmacokinetics,ritterazines, steroidal alkaloids,structure activity relationship,biochemistry,molecular biology,drug discovery,organic chemistry,sdg 14 - life below water ,/dk/atira/pure/subjectarea/asjc/1300/1303 |
| Faculty \ School: | Faculty of Science > School of Pharmacy (former - to 2024) |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 13 Aug 2024 17:30 |
| Last Modified: | 01 Oct 2024 03:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96243 |
| DOI: | 10.1016/j.bioorg.2024.107654 |
Actions (login required)
 |
View Item |