Semi-synthetic DMC derivatives were synthesised and displayed biological potency against various cancer cell lines.

The emergence of SARS-CoV-2 in December 2019 has become a global issue due to the continuous upsurge in patients and the lack of drug efficacy for treatment. SARS-CoV-2 3CLPro is one of the most intriguing biomolecular targets among scientists worldwide for developing antiviral drugs due to its relevance in viral replication and transcription. Herein, we utilized computer-assisted drug screening to investigate 326 natural products from Thai traditional plants using structure-based virtual screening against SARS-CoV-2 3CLPro. Following the virtual screening, the top 15 compounds based on binding energy and their interactions with key amino acid Cys145 were obtained. Subsequently, they were further evaluated for protein–ligand complex stability via molecular dynamics simulation and binding free energy calculation using molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) approaches. Following drug-likeness and ADME/Tox assessments, seven bisbenzylisoquinolines were obtained, including neferine (3), liensinine (4), isoliensinine (5), dinklacorine (8), tiliacorinine (13), 2′-nortiliacorinine (14), and yanangcorinine (15). These compounds computationally showed a higher binding affinity than native N3 and GC-373 inhibitors and attained stable interactions on the active site of 3CLpro during 100 ns in molecular dynamics (MD) simulation. Moreover, the in vitro enzymatic assay showed that most bisbenzylisoquinolines could experimentally inhibit SARS-CoV-2 3CLPro. To our delight, isoliensinine (5) isolated from Nelumbo nucifera demonstrated the highest inhibition of protease activity with the IC50 value of 29.93 μM with low toxicity on Vero cells. Our findings suggested that bisbenzylisoquinoline scaffolds could be potentially used as an in vivo model for the development of effective anti-SARS-CoV-2 drugs.

Although cisplatin is a first-line chemotherapy drug for head and neck squamous cell carcinoma (HNSCC), its therapeutic efficacy is limited owing to serious side effects and acquired drug resistance. This study determined whether combining pentagalloyl glucose (PGG) and cisplatin enhanced their anti-tumor activities on HNSCC cell lines. We investigated the anticancer effect of PGG combined with cisplatin in 2D and 3D multicellular spheroid cell culture. The results revealed that PGG combined with cisplatin inhibited cell viability and produced synergistic effects. PGG potentiates the anticancer effect of cisplatin by promoting apoptosis and inhibiting cell migration. The western blot and molecular docking analysis revealed that the synergistic effect of the combination treatment may be related to the PGG-mediated reduced expression of phosphorylated STAT3 and phosphorylated Akt. Furthermore, we found that the combined treatment of PGG and cisplatin’s effect on 3D multicellular spheroid size was more potent than the monotherapies. Our findings indicated that the combination therapy of PGG and cisplatin synergistically inhibited HNSCC cancer cell viability and induced apoptosis in 2D and 3D models. The present results suggested that PGG may be a promising adjunct drug used with cisplatin for a practical therapeutic approach to head and neck cancer.

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC), a natural product derived from Syzygium nervosum A. Cunn. ex DC., was investigated for its inhibitory activities against various cancer cell lines. In this work, we investigated the effects of DMC and available anticervical cancer drugs (5-fluorouracil, cisplatin, and doxorubicin) on three human cervical cancer cell lines (C-33A, HeLa, and SiHa). DMC displayed antiproliferative cervical cancer activity in C-33A, HeLa, and SiHa cells, with IC50 values of 15.76 ± 1.49, 10.05 ± 0.22, and 18.31 ± 3.10 µM, respectively. DMC presented higher antiproliferative cancer activity in HeLa cells; therefore, we further investigated DMC-induced apoptosis in this cell line, including DNA damage, cell cycle arrest, and apoptosis assays. As a potential anticancer agent, DMC treatment increased DNA damage in cancer cells, observed through fluorescence inverted microscopy and a comet assay. The cell cycle assay showed an increased number of cells in the G0/G1 phase following DMC treatment. Furthermore, DMC treatment-induced apoptosis cell death was approximately three- to four-fold higher compared to the untreated group. Here, DMC represented a compound-induced apoptosis for cell death in the HeLa cervical cancer cell line. Our findings suggest that DMC, a phytochemical agent, is a potential candidate for antiproliferative cervical cancer drug development.

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The quinazolinone scaffold is found in natural products and biologically active compounds, including inflammatory inhibitors. Major proteins or enzymes involved in the inflammation process are regulated by the amount of gene expression. Quinazolinone derivatives were investigated and developed against the inflammatory genes cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cell line. The mRNA expressions were measured using a real-time quantitative polymerase chain reaction (RT-qPCR). Quinazolinone compounds at 62.5 μM demonstrated anti-COX-2 and anti-IL-1β mRNA expressions down to 0.50% and 3.10% gene expression, respectively, via inhibition of nuclear factor κB (NF-κB). Molecular docking was performed to explain the interaction between the binding site and the developed compounds as well as the structure−activity relationship of the quinazolinone moiety.

Correction for ‘Synthesis and application of methyl itaconate–anthracene adducts in configuration assignment of chiral secondary alcohols by 1H NMR’ by Puracheth Rithchumpon et al., Org. Biomol. Chem., 2021, DOI: 10.1039/D1OB01387D.

This work investigates the high catalytic activity of bi‐functional lithium N‐heterocyclic carbene (bisLiNHCs) complexes in bulk ring‐opening polymerization (ROP) of ε‐caprolactone (ε‐CL) monomer at room temperature. The study employs a bulk ROP technique using tetramethylene‐tethered bis[N‐(N′‐alkyl/arylimidazolium)] bishexafluorophosphate (bis[Bim][PF6]), benzyl alcohol (BnOH), and n‐butyl lithium (nBuLi) in molar ratios of 1:2:4. The results show that 1,4‐bisLiNHC (3a) has the highest catalytic capability, producing the highest molecular weight of PCL with acceptable dispersity in only 93 s (59 361 g mol−1, Đ = 1.8). However, longer and aromatic linker chains (3b‐3g) are found to be less effective due to the increased steric effect for complex formation with the monomer, leading to longer reaction times and lower molecular weight PCL with wider dispersity. Additionally, the study conducts a mechanistic analysis using the DFT method with B3LYP (6‐31G(d,p)) as the basis set. The most plausible mechanism proposed involves continuous and coordinated insertion with low energy barriers.