Original Article

Discovery of Tyrosinase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation

Wang, Guan; Li, Jin; Pan, Xiao-Li; Bu, Fa-Qian; Zhu, Yu-Meng; Wang, Ao-Xue; Ouyang, Liang

This study reported the use of homology modeling and multistep structure-based virtual screening for the discovery of novel tyrosinase inhibitors. In this study, 10 initial potential hits (compounds T1–T10) were evaluated for enzyme inhibition and kinetic study, with kojic acid being used as a control. Among them, the IC₅₀ values of both T1 (11.56 ± 0.98 µmol/L) and T5 (18.36 ± 0.82 µmol/L) were superior to that of kojic acid (23.12 ± 1.26 µmol/L). Moreover, T1 and T5 were also identified as the effective noncompetitive tyrosinase inhibitors by the subsequent kinetic study. T1 and T5 may represent the promising drug candidates for hyperpigmentation therapy in pharmaceutical fields, as well as the effective whitening agents in cosmetic applications.

Synthesis and Biological Evaluation of a Series of Novel 1-(3-((6-Fluoropyridin-3-yl)oxy)propyl)piperazines as Dopamine/Serotonin Receptor Agonists

Multitarget approach may provide a double bonus for the treatment of Parkinson’s disease (PD). In this study, 20 novel 1-(3-((6-fluoropyridin-3-yl)oxy)propyl)piperazine derivatives were designed and synthesized.  Among them, compounds 7b and 34c showed agonistic activities on D2/D3/5-HT_1A receptors. The EC₅₀ value of 7b for D2/D3/5-HT1A receptor were 0.9/19/2.3 nmol/L, respectively; and the EC₅₀ value of 34c for D2/D3/5-HT1A receptor were 3.3/10/1.4 nmol/L, respectively. In addition, 34c exhibited good metabolic stability (the half-life T_1/2 = 159.7 minutes) in vitro, which is of great significance for the further exploration of multitarget anti-PD drugs.

Design, Synthesis, and Evaluation of Benzoheterocyclic-Containing Derivatives as Novel HDAC1 Inhibitors

Jiao, Min-Ru; Han, Bo; Gu, Xiu; Zhang, Hao; Wang, Ai-Ping; Zhang, Qing-Wei

In this study, the synthesis and biological evaluation of a variety of benzoheterocyclic containing benzamide derivatives were described. Some of these compounds were proved to inhibiting the activity of histone deacetylase 1 (HDAC1) with IC₅₀ values below the micromolar range, retarding proliferation of several human cancer cells, and surprisingly, not possessing toxicity to human normal cells and hERG K⁺ ion channels. Among those compounds, 3c was the most potent and efficacious derivative. Compound 3c was orally active and displayed excellent in vivo antitumor activity in a HCT-116 xenograft mice model.

Senna podocarpa Emulgel: A Herbal Alternative for Chemical Burn Wound Treatment

Isaac, Johnson Ajeh; Daburi, Aisha; Ifeanyi, Benneth; Ben-Umeh, Kenechukwu Chijioke; Adedokun, Abiodun Abigail; Builders, Philip

Senna podocarpa (SP) leaves are used in folk medicines for treatment of burns and wounds aspoultices on wound surface. In this work, phytochemical screening showed the presence of alkaloids, saponins, tannins, cardiac glycosides, flavonoids, anthraquinones, and phenols within the hydro-ethanolic extract of SP leaves, and high flavonoid content is believed to be responsible for its healing attributes. This work also suggested the benefit of its preparation as an emulgel in wounding treatment.

Highlights and Comments

KRAS Q61H Mutation Confers Cancer Cells with Acquired Resistance to SHP2 Inhibition

Song, Yi-Hui; Yang, Xin-Yu; Yu, Bin

This study suggested that targeting the upstream effectors such as RTKs, SHP2, and SOS may be ineffective in KRAS Q61H-mutated tumor, whereas targeting the downstream signaling molecules of KRAS (e.g., RAF, MEK, ERK, PI3K, AKT, mTOR) may be a feasible approach for the treatment of KRAS Q61H-driven cancers. Combination of KRAS inhibitor and downstream target inhibitors may show therapeutic promise in tumors harboring KRAS Q61H mutation.