New amide conjugates of hydroxycinnamic acids (HCAs) and the known antineoplastic 5,11-dimethyl-5H-indolo[2,3-b]quinoline (DiMIQ), an analog of the natural alkaloid neocryptolepine, were synthesized and tested in vitro for anticancer activity. The compound 9-[((2-hydroxy)cinnamoyl)amino]-5,11-dimethyl-5H-indolo[2,3-b]quinoline (2), which contains the ortho-coumaric acid fragment, demonstrated dose-dependent effectiveness against both normal BxPC-3 and metastatic AsPC-1 pancreatic cancer cells. The IC50 values for AsPC-1 and BxPC-3 were 336.5 nM and 347.5 nM, respectively, with a selectivity index of approximately 5 for both pancreatic cancer cells compared to normal dermal fibroblasts. Conjugate 2 did not exhibit any hemolytic activity against human erythrocytes at the tested concentration. Computational studies were performed to predict the pharmacokinetic profile and potential mechanism of action of the synthesized conjugates. These studies focused on the ADME properties of the conjugates and their interactions with DNA, as well as DNA-topoisomerase alpha and beta complexes. All of the conjugates studied showed approximately one order of magnitude stronger binding to DNA compared to the reference DiMIQ, and approximately two orders of magnitude stronger binding to the topoisomerase II-DNA complex compared to DiMIQ. Conjugate 2 was predicted to have the strongest binding to the enzyme-DNA complex, with a Ki value of 2.8 nM.

\'Epigenetic\' regulation of genes via post-translational modulation of proteins is a wellexplored approach for disease therapies, particularly cancer chemotherapeutics. Histone deacetylases (HDACs) are one of the important epigenetic targets and are mainly responsible for balancing the acetylation/deacetylation of lysine amino acids on histone/nonhistone proteins along with histone acetyltransferase (HAT). HDAC inhibitors (HDACIs) have become important biologically active compounds for the treatment of cancers due to cell cycle arrest, differentiation, and apoptosis in tumor cells, thus leading to anticancer activity. Out of the four classes of HDAC, i.e., Class I, II, III, and IV, HDACIs act on Class IV (Zinc dependent HDAC), and various FDA-approved drugs belong to this category. The required canonical pharmacophore model (zinc-binding group, surface recognition cap, and appropriate linker) supported by HDACIs, various heterocyclic moieties containing compounds exhibiting HDAC inhibitory activity, and structure-activity relationship of different synthetic derivatives reported during the last twelve years have been summarized in this review.

A series of novel inulin derivatives were designed and synthesized by the introduction of amino heterocyclic moieties onto carboxymethyl inulin with the aid of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide. The target products were prepared via three - step chemical synthesis, and structures were identified by FTIR and 1H NMR spectroscopy. Antioxidant activities of inulin derivatives including DPPH - radical scavenging assay, superoxide - radical scavenging assay, hydroxyl - radical scavenging assay, and reducing power were estimated. Meanwhile, their antifungal activities, including Colletotrichum lagenarium and Botrytis cinerea, were also explored by hyphal measurement. In particular, inulin derivatives bearing heterocyclic moieties exhibited a remarkable improvement over inulin on antioxidant and antifungal activities, and their bioactivities decreased roughly in the order of 2ATCMI > 4APCMI > 3APCMI > 2APCMI > 3ATCMI > CMI > inulin. Furthermore, the cytotoxicities of inulin derivatives against L929 cells were evaluated by CCK-8 in vitro, and all samples showed weak cytotoxicities. In a nutshell, the paper provides a practical approach to synthesize novel inulin derivatives with dramatically enhanced bioactivity and good biocompatibility. The product described in paper might serve as a new leading structure for further design of antioxidants or antifungal agents in biomedicine, cosmetics, and other fields.

Heterocyclic building blocks possessing ethylene spacer and amine functionality such as 1-(2-aminoethyl)piperidine (1,2-AEPi), 2-(2-aminoethyl)pyridine (2,2-AEPy) and 1-(2-aminoethyl)pyrrolidine (1,2-AEPr) were reacted with tetracyanoquinodimethane (TCNQ) to give disubstituted compounds namely bis-(1-(2-aminoethyl)piperidino)dicyanoquinodimethane (1), bis-(2-(2-aminoethyl)pyridino)dicyanoquinodimethane (2) and bis-(1-(2-aminoethyl)pyrrolidino)dicyanoquinodimethane (3). Utilization of 1,2-AEPi, 2,2-AEPy and 1,2-AEPr as disubstituents on TCNQ has resulted in interesting crystal structures. Inter- and intramolecular hydrogen-bond mediated and expanded supramolecular structures were observed in the lattices of the crystals. Strong fluorescence was observed in solids and solutions. (2) showed a strong second harmonic generation (SHG) whereas (1) and (3) were found to be SHG inactive. All compounds possess good thermal stabilities.