Herein, we explore the Kisspeptin 1 Receptor (KISS1R) as a potential therapeutic target for the restoration of drug sensitivity in Triple-Negative Breast Cancer (TNBC) clinical settings. Recent functional studies of KISS1R have revealed that the receptor plays a pro-metastatic role in TNBC. By the promotion of multidrug resistance proteins, KISS1R has been shown to regulate TNBC drug resistance. Chemotherapy remains the standard clinical procedure for the treatment of TNBC, however the ability of cancer cells to become resistant to chemotherapy continues to be a major obstacle. Thus, there is an intense interest around the development of novel, synthetic agents, which may synergise with current breast cancer therapeutic options. In this review, we aim to highlight the pro-metastatic mechanism of KP/KISS1R signalling and the therapeutic potential surrounding the receptor's attenuation. In addition, we explore the modes of KISS1R inhibition by drawing upon peptidic based antagonists, agonists and small molecule hit compounds.

Two fluorescent molecularly imprinted polymers (MIPs) were developed for pepsin enzyme utilising fluorescein and rhodamine b. The main difference between both dyes is the presence of two (diethylamino) groups in the structure of rhodamine b. Consequently, we wanted to investigate the effect of these functional groups on the selectivity and sensitivity of the resulting MIPs. Therefore, two silica-based MIPs for pepsin enzyme were developed using 3-aminopropyltriethoxysilane as a functional monomer and tetraethyl orthosilicate as a crosslinker to achieve a one-pot synthesis. Results of our study revealed that rhodamine b dyed MIPs (RMIPs) showed stronger binding, indicated by a higher binding capacity value of 256 mg g −1 compared to 217 mg g −1 for fluorescein dyed MIPs (FMIPs). Moreover, RMIPs showed superior sensitivity in the detection and quantitation of pepsin with a linear range from 0.28 to 42.85 µmol L −1 and a limit of detection (LOD) as low as 0.11 µmol L −1. In contrast, FMIPs covered a narrower range from 0.71 to 35.71 µmol L −1 , and the LOD value reached 0.34 µmol L −1 , which is three times less sensitive than RMIPs. Finally, the developed FMIPs and RMIPs were applied to a separation-free quantification system for pepsin in saliva samples without interference from any cross-reactors.

Herein, we present a synthetic compound library comprising of 13 structurally diverse heterocyclic monosquarate-amide derivatives. The compounds featured in this library were designed as potential bioisosteric replacements carboxylic acid moiety’s. A good selection of the compounds presented exhibit unique molecular architecture and have shown promising results following in silico evaluation of ‘druglike properties’ using Swiss ADME. The research presented in this work focuses on the preparation of derivatives of 3,4-dihydroxycyclobut-3-ene-1,2-dione, a known carboxylic acid bioisostere.

Herein, we present a synthetic compound library comprising of 28 anilino and benzylamino monosquarate-amide derivatives. Members of this library were designed as bioisosteric replacements for groups such as the ubiquitous carboxylic acid moiety. Further to their synthesis, we have shown the potential of these chemical building blocks for the generation of additional novel compounds. This work forms part of our efforts aimed at the assembly of 96-well plates loaded with bioisosteric analogues that may be used to enrich drug discovery programs. The research presented in this work focuses on the chemistry of 3,4-dihydroxycyclobut-3-ene-1,2-dione, a known carboxylic acid bioisostere.