Research progress in the biological activities of 3,4,5-trimethoxycinnamic acid (TMCA) derivatives

Abstract

TMCA (3,4,5-trimethoxycinnamic acid) ester and amide are privileged structural scaffolds in drug discovery which are widely distributed in natural products and consequently produced diverse therapeutically relevant pharmacological functions. Owing to the potential of TMCA ester and amide analogues as therapeutic agents, researches on chemical syntheses and modifications have been carried out to drug-like candidates with broad range of medicinal properties such as antitumor, antiviral, CNS (central nervous system) agents, antimicrobial, anti-inflammatory and hematologic agents for a long time. At the same time, SAR (structure-activity relationship) studies have draw greater attention among medicinal chemists, and many of the lead compounds were derived for various disease targets. However, there is an urgent need for the medicinal chemists to further exploit the precursor in developing chemical entities with promising bioactivity and druggability. This review concisely summarizes the synthesis and biological activity for TMCA ester and amide analogues. It also comprehensively reveals the relationship of significant biological activities along with SAR studies.

Keywords: 3,4,5-Trimethoxycinnamic acid; Antimicrobial agents; Antitumor agents; Antiviral agents; CNS agnets; Hematologic agents; SAR; TMCA derivatives; anti-inflammatory agents.

Graphical abstract

Fig. 1

Structure of 3,4,5-trimethoxycinnamic acid (TMCA).

Fig. 2

Drug design strategy: based on Combination of Traditional Chinese Medicine Chemistry (CTCMC).

Fig. 3

TMCA esters isolated from P. tenuifolia.

Fig. 4

TMCA esters isolated from other natural products.

Fig. 5

Structure of piplartine.

Fig. 6

Structure of synthetic TMCA ester derivatives as antitumor agents (S1-S10).

Fig. 7

Structure of synthetic TMCA amide derivatives as antitumor agents (S11-S29).

Fig. 8

Structure of synthetic TMCA derivatives as antivival agents (S30-S35).

Fig. 9

Structure of synthetic TMCA ester derivatives as CNS agents (S36-S39).

Fig. 10

Structure of synthetic TMCA amide derivatives as CNS agents (S40-S48).

Fig. 11

Structure of synthetic TMCA amide derivatives as antimicrobial agents (S49-S54).

Fig. 12

Structure of synthetic TMCA amide derivatives as antimicrobial agents (S55-S59).

Fig. 13

Structure of synthetic TMCA ester derivatives as anti-inflammatory agents (S60-S62).

Fig. 14

Structure of synthetic TMCA amide derivatives as anti-inflammatory agents (S63-S67).

Fig. 15

Structure of synthetic TMCA derivatives as hematologic agents (S68-S71).

Fig. 16

Structure of synthetic TMCA derivatives for other activities (S72-S74).