Details
| Original language | English |
|---|---|
| Article number | e202303730 |
| Journal | CHEMISTRYSELECT |
| Volume | 8 |
| Issue number | 46 |
| Publication status | Published - 11 Dec 2023 |
| Externally published | Yes |
Abstract
Despite the continued efforts and advancements in anti-cancer drug discovery, cancer is still considered as one of the leading causes of mortality globally. Hence, the discovery of novel chemotherapeutic agents that displayed a prominent effect against cancer is a pressing need. In this study, an expeditious cascade was used to access a pilot library of indolopyrazine fused to imidazole and pyrimidinone heterocyclic scaffolds. The synthetic strategy utilized a cascade reaction that combined Mannich with aza-Michael addition reactions followed by coupling with a variety of amines. Phenotypic screening of the developed library against HCT116 colon and MCF-7 breast cancer cell lines identified chemotypes that formed the basis for hit-to-lead development of anti-cancer agents. The intriguing architecture and scope of functional variability of these types of pentacyclic molecules made them appropriate motifs for the development of lead drug candidates.
Keywords
- Anticancer, Aza-Michael addition, Evodiamine, Indolopyrazines, Mannich reaction
ASJC Scopus subject areas
Sustainable Development Goals
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In: CHEMISTRYSELECT, Vol. 8, No. 46, e202303730, 11.12.2023.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Divergent Strategy for the Synthesis of Indolopyrazines Fused to Benzopyrimidinones and Benzimidazoles: Identification of Antiproliferative Molecules
AU - Alkubaisi, Bilal O.
AU - Sebastian, Anusha
AU - Bauer, Maximilian
AU - Sultan, Shaista
AU - El‐Awady, Raafat
AU - Wehbe, Ayeh
AU - Yassin, Mariam
AU - Vunnam, Srinivasulu
AU - El‐Gamal, Mohammed I.
AU - Al‐Tel, Taleb H.
N1 - Publisher Copyright: © 2023 Wiley-VCH GmbH.
PY - 2023/12/11
Y1 - 2023/12/11
N2 - Despite the continued efforts and advancements in anti-cancer drug discovery, cancer is still considered as one of the leading causes of mortality globally. Hence, the discovery of novel chemotherapeutic agents that displayed a prominent effect against cancer is a pressing need. In this study, an expeditious cascade was used to access a pilot library of indolopyrazine fused to imidazole and pyrimidinone heterocyclic scaffolds. The synthetic strategy utilized a cascade reaction that combined Mannich with aza-Michael addition reactions followed by coupling with a variety of amines. Phenotypic screening of the developed library against HCT116 colon and MCF-7 breast cancer cell lines identified chemotypes that formed the basis for hit-to-lead development of anti-cancer agents. The intriguing architecture and scope of functional variability of these types of pentacyclic molecules made them appropriate motifs for the development of lead drug candidates.
AB - Despite the continued efforts and advancements in anti-cancer drug discovery, cancer is still considered as one of the leading causes of mortality globally. Hence, the discovery of novel chemotherapeutic agents that displayed a prominent effect against cancer is a pressing need. In this study, an expeditious cascade was used to access a pilot library of indolopyrazine fused to imidazole and pyrimidinone heterocyclic scaffolds. The synthetic strategy utilized a cascade reaction that combined Mannich with aza-Michael addition reactions followed by coupling with a variety of amines. Phenotypic screening of the developed library against HCT116 colon and MCF-7 breast cancer cell lines identified chemotypes that formed the basis for hit-to-lead development of anti-cancer agents. The intriguing architecture and scope of functional variability of these types of pentacyclic molecules made them appropriate motifs for the development of lead drug candidates.
KW - Anticancer
KW - Aza-Michael addition
KW - Evodiamine
KW - Indolopyrazines
KW - Mannich reaction
UR - http://www.scopus.com/inward/record.url?scp=85179347669&partnerID=8YFLogxK
U2 - 10.1002/slct.202303730
DO - 10.1002/slct.202303730
M3 - Article
VL - 8
JO - CHEMISTRYSELECT
JF - CHEMISTRYSELECT
SN - 2365-6549
IS - 46
M1 - e202303730
ER -