Conformationally based design of macrocycles as antitumor agents.
A key feature for any chemotherapeutic agent is a favorable conformation when it is presenting itself to its intended target. Numerous macrocycles have been identified as having antitumor activity and have been a source of lead compounds in anticancer research. The macrocyclic scaffold restricts bond rotation, therefore macrocycles maintain a relatively rigid conformation compared to their linear counterparts. This review discusses recent progress in the development of macrocyclic versions of linear compounds with known antitumor activity, and describes how restrictions in molecular conformation affect tumor inhibition.
Singh
Erinprit K
EK
San Diego State University, Department of Chemistry and Biochemistry, 5500 Campanile Drive, San Diego, CA 92182, USA.
Sellers
Robert P
RP
Alexander
Leslie D
LD
McAlpine
Shelli R
SR
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D047028:Macrocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047028:Macrocyclic Compounds; D010455:Peptides