Recently, there has been a renewed interest in the natural-products-inspired drugs. Quebrachitol (QCT) is one of naturally occurring optically active cyclitols that has now received considerable attention. Until the last decade, it came to be a starting point for the lead discovery. In this review, we had a discussion on the basic research of QCT, including its source, structure, properties, and the recent advances on its application. The biological activities and QCT-inspired leads that are potentially effective for treating human diseases were also discussed.

Tankyrases (TNKS), key transmitters in the Wnt signaling pathway which is very conservative in evolution, are vital targets as they are overexpressed widely in many cancers. In this work, 5 inhibitors with novel structures have been discovered and validated using the ligand-based (pharmacophore) virtual screening, docking study, and Luciferase reporter assays for Wnt signaling. Among them, PYL-1, in particular, was the most potent inhibitor with an IC50 value of 9.56 μM against Wnt signaling. The analysis of binding modes was performed to further understand the vital interactions between inhibitors and TNKS 2, and the five hits belong to dual site inhibitors. This work could be helpful for the design and development of novel dual binders as TNKS inhibitors.

Tankyrases (TNKS), key transmitters in the Wnt signaling pathway which is very conservative in evolution, are vital targets as they are overexpressed widely in many cancers. In this work, 5 inhibitors with novel structures have been discovered and validated using the ligand-based (pharmacophore) virtual screening, docking study, and Luciferase reporter assays for Wnt signaling. Among them, PYL-1, in particular, was the most potent inhibitor with an IC50 value of 9.56 μM against Wnt signaling. The analysis of binding modes was performed to further understand the vital interactions between inhibitors and TNKS 2, and the five hits belong to dual site inhibitors. This work could be helpful for the design and development of novel dual binders as TNKS inhibitors.

The new melokhanines A–J (1–10) and 22 known (11–32) alkaloids were isolated from the twigs and leaves of Melodinus khasianus. The new compounds and their absolute configurations were elucidated by extensive analysis of spectroscopic, X-ray diffraction, and computational data. Melokhanine A (1), composed of a hydroxyindolinone linked to an octahydrofuro[2,3-b]pyridine moiety, is an unprecedented monoterpenoid indole alkaloid. Melokhanines B–H (2–8) possess a new 6/5/5/6/6 pentacyclic indole alkaloid skeleton. Alkaloids 1–16, 25–27, 31, and 32 showed the best antibacterial activity against Pseudomonas aeruginosa (MIC range 2–22 μM). Among the seven dermatophytes tested, compound 1 showed significant inhibitory activity against Microsporum canis, M. ferrugineum, and Trichophyton ajelloi (MIC range 38–150 μM), i.e., half the efficacy of the positive control, griseofulvin.

Four pairs of enantiomeric hypoxanthine analogues (1, 2, 5 and 6), two pairs of enantiomeric adenine analogues (3 and 4), two pyrazines, aspongpyrazines A (7) and B (8), and a pair of glycerides ((+)-9 and (−)-9), along with twenty-eight known substances were isolated from the insect Aspongopus chinensis. The structures of the new natural products were assigned by using spectroscopic and computational methods. Chiral HPLC was used to separate the (−)- and (+)-antipodes of 1–6, and 9. Several of the new, A. chinensis derived natural products were found to promote proliferation of neural stem cells (NSCs) at a concentration of 10 μM.

The unusual fused β-lactone vibralactone was isolated from cultures of the basidiomycete Boreostereum vibrans and has been shown to significantly inhibit pancreatic lipase. In this study, a structure-based lead optimization of vibralactone resulted in three series of 104 analogs, among which compound C1 exhibited the most potent inhibition of pancreatic lipase, with an IC50 value of 14 nM. This activity is more than 3000-fold higher than that of vibralactone. The effect of compound C1 on obesity was investigated using high-fat diet (HFD)-induced C57BL/6 J obese mice. Treatment with compound C1 at a dose of 100 mg/kg significantly decreased HFD-induced obesity, primarily through the improvement of metabolic parameters, such as triglyceride levels.

The bioassay-guided chemical investigation of the stems of Dendrobium fimbriatum Hook led to the isolation of seven first reported bibenzyl dimers with a linkage of a methylene moiety, fimbriadimerbibenzyls A–G (1–7), together with a new dihydrophenanthrene derivative (S)-2,4,5,9-tetrahydroxy-9,10-dihydrophenanthrene (8) and thirteen known compounds (9–21). The structure of the new compound was established by spectroscopic analysis. Biological evaluation of bibenzyl derivatives against five human cell lines indicated that seven of those compounds exhibited broad-spectrum and cytotoxic activities with IC50 values ranging from 2.2 to 21.2 μM. Those rare bibenzyl dimers exhibited cytotoxic activities in vitro and the cytotoxicity decreased as the number of oxygen-containing groups in the structure decreases.

•The different methods studied on the global aromaticity, π aromaticity and σ aromaticity of the classical heterobenzenes.•The π aromatic order of the group five hetrobenzenes (C6H6 > C5H5N > C5H5P > C5H5As > C5H5Sb > C5H5Bi) is established firmly.•The different densities of σ bonds from the center of cycle predict well the discrepancies between ELFσ and NICS(max)σzz.Aromaticity is a key concept in physical organic chemistry. The aromatic order of the classic heterobenzenes was reported in experiment early. However, the unambiguous criteria used to validate the aromaticity of that were controversial or inadequate in theory. In this work, the global aromaticity of the compounds has been studied using the ELF, NICS and ISE. NICS(max)zz was calculated based on the maximum NICS contribution to the out-of-plane zz tensor component. Two types of bonds are observed. The correlations between NICS(max)σzz and NICS(max)πzz with respect to aromaticity are demonstrated, specifically between NICS(max)πzz and ELFπ (cc = 0.98) for π bonds. For σ bonds, the different electron delocalization of σ bonds out of the plane of the ring predicted well the discrepancies between NICS(max)σzz and ELFσ. The σ aromatic order of the classic heterobenzenes (C5H5N > C6H6 > C5H5P > C5H5As > C5H5Bi, C5H5Sb) was proved via the level of electronic delocalization.Graphical abstractThe global aromaticity and π aromaticity of the classic heterobenzenes (C6H6 > C5H5N > C5H5P > C5H5As > C5H5Sb > C5H5Bi) is established firmly. For σ aromaticity, the technique of ELFσ permits overall assignment of σ aromatic character of the group five heterobenzenes. Both FLFπ and NICS(max)πzz are easily and efficiently applied to decide π aromatic character, and performed well statistically (cc = 0.98). Both techniques demonstrated that the value order of π aromatic is of the same order as the global aromaticity.

Coiled-coils are well known protein–protein interaction motifs, with the leucine zipper region of activator protein-1 (AP-1) consisting of the c-Jun and c-Fos proteins being a typical example. Molecular dynamics (MD) simulations using the MM/GBSA method have been used to predict the free energy of interaction of these proteins. The influence of force field polarisation and capping on the predicted free energy of binding of complexes with different electrostatic environments (net charge) were investigated. Although both force field polarisation and peptide capping are important for the prediction of the absolute free energy of binding, peptide capping has the largest influence on the predicted free energy of binding. Polarisable simulations appear better suited to determine structural properties of the complexes of these proteins while non-polarisable simulations seem to give better predictions of the associated free energies of binding.

•Three HQSAR, CoMFA and CoMSIA methodologies were used in this study.•CoMSIA model shows the best correlation and satisfactory predictability.•QSAR models yield key structural modification information to improve bioactivity.•Further understanding of the vital interactions between receptor and ligands.The inhibition of β-secretase (BACE1) is currently the main pharmacological strategy available for Alzheimer’s disease (AD). 2D QSAR and 3D QSAR analysis on some cyclic sulfone hydroxyethylamines inhibitors against β-secretase (IC50: 0.002–2.75 μM) were carried out using hologram QSAR (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) methods. The best model based on the training set was generated with a HQSAR q2 value of 0.693 and r2 value of 0.981; a CoMFA q2 value of 0.534 and r2 value of 0.913; and a CoMSIA q2 value of 0.512 and r2 value of 0.973. In order to gain further understand of the vital interactions between cyclic sulfone hydroxyethylamines and the protease, the analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the BACE1. The final QSAR models could be helpful in the design and development of novel active BACE1 inhibitors.

An efficient hydrogen bonding-guided ring-closing metathesis (RCM) reaction of sterically demanding homoallyl 2-(hydroxymethyl)acrylates catalyzed by the Hoveyda–Grubbs 2nd generation catalyst was developed and the reaction mechanism was explored. Adding a substituent to the hydroxymethyl group in this scaffold resulted in a class of challenging RCM substrates, although usable yields could be obtained. However, substrates bearing a 1-oxygenated alkyl group on the homoallylic carbon gave excellent RCM yields, providing a practical solution. Experimental and computational evidence indicated an unusual directing effect of OH⋯Cl hydrogen bonding between the substrate and Ru catalyst, which guides Ru to interact with the electron-deficient, more hindered acrylic CC bond and thus triggers the RCM process.