Recent advances in construction of small molecule-based fluorophore-drug conjugates

Abstract

As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs’ transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.

Late‐Stage Amination of Drug‐Like Benzoic Acids: Access to Anilines and Drug Conjugates through Directed Iridium‐Catalyzed C−H Activation

“…A biotinylated Tranilast analogue was prepared in a three‐step protocol, providing compound 3 yc in a 63 % overall yield. Small‐molecule‐based fluorophore–drug conjugates represent a valuable class of tool compounds for real‐time monitoring of drug delivery and distribution [7a] . The synthesis of molecular imaging tool compounds was exemplified with the Fluorescein‐tagged compound 3 yd .…”

Turning a Quinoline-based Steroidal Anticancer Agent into Fluorescent Dye for its Tracking by Cell Imaging

“…Deciphering the mechanism of action (MoA) of a bioactive molecule identified from a phenotypic screening approach is a key step to support its further pharmaceutical development into a drug. − Cell imaging using a fluorescent version of a bioactive molecule is an enabling technology toward this end. , However, the nature and size of the labeling fluorophore attached to a small molecule often interfere with its ability to bind to the biological target of interest, thus limiting the validity of inherent cell imaging. − Ideally, the fluorophore used should be as small as possible to most realistically reflect the original unlabeled molecule’s behavior . This is particularly true in the case of a lead compound identified from a phenotypic approach when its related biological target is unknown, and thus the assumption that the fluorophore should not interfere with this target cannot be virtually estimated.…”

“…1−3 Cell imaging using a fluorescent version of a bioactive molecule is an enabling technology toward this end. 4,5 However, the nature and size of the labeling fluorophore attached to a small molecule often interfere with its ability to bind to the biological target of interest, thus limiting the validity of inherent cell imaging. 6−8 Ideally, the fluorophore used should be as small as possible to most realistically reflect the original unlabeled molecule's behavior.…”

Accurate Quantification of Sulfonamide Metabolites in Goat Meat: A New Strategy for Minimizing Interaction between Sheep Serum Albumin and Sulfonamide Metabolites

“…Binding quenching methods are static quenching and dynamic quenching . As a hypothetical dynamic quenching process, the quenching rate constants were determined using the Stern–Volmer equation where F and F 0 are the fluorescence intensity in the presence and absence of sulfamerazine, respectively, K q is the quenching rate constant, K sv is the Stern–Volmer constant, τ 0 is the fluorescence lifetime of sheep serum albumin in the absence of sulfamerazine (10 –8 s), and [Q] is the concentration of sulfamerazine.…”

“…Binding quenching methods are static quenching and dynamic quenching. 23 As a hypothetical dynamic quenching process, the quenching rate constants were determined using the Stern−Volmer equation ) where F and F 0 are the fluorescence intensity in the presence and absence of sulfamerazine, respectively, K q is the quenching rate constant, K sv is the Stern−Volmer constant, τ 0 is the Using eq 5, the quenching constant K q was 1.83 × 10 12 L mol −1 s −1 and K sv was 1.83 × 10 4 L mol −1 s −1 . The obtained K q values are on a scale of 10 12 L mol −1 s −1 , which far exceeds the diffusion-controlled rate constant in aqueous solution, i.e., 2.0 × 10 10 L mol −1 s −1 , confirming that quenching does not involve a dynamic diffusion process but occurs statically in complex.…”