Cephalostatins and ritterazines: Distinctive dimeric marine-derived steroidal pyrazine alkaloids with intriguing anticancer activities.

Autor: Tammam MA; Department of Biochemistry, Faculty of Agriculture, Fayoum University, Fayoum 63514, Egypt., Gamal El-Din MI; Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, 11566 Cairo, Egypt; Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk NR4 7UQ, UK., Aouidate A; School of Applied Sciences-Ait Melloul, Ibn Zohr University, Agadir, Morocco., El-Demerdash A; School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7UH, UK; Department of Biochemistry and Metabolism, the John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK; Division of Organic Chemistry, Department of Chemistry, Faculty of Sciences, Mansoura University, Mansoura 35516, Egypt. Electronic address: a_eldemerdash83@mans.edu.eg.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Oct; Vol. 151, pp. 107654. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1016/j.bioorg.2024.107654
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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