Lung cancer is one of the most common cancers and has a high mortality rate. Due to its high incidence, the clinical management of the disease remains a major challenge. Several reports have documented a relationship between the phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway and lung cancer. The recognition of this pathway as a notable therapeutic target in lung cancer is mainly due to its central involvement in the initiation and progression of the disease. Interest in using natural and synthetic medications to target these signaling pathways has increased in recent years, with promising results in vitro, in vivo, and in clinical trials. In this review, we focus on the current understanding of PI3K/AKT/mTOR signaling in tumor development. In addition to the signaling pathway, we highlighted the therapeutic potential of recently developed PI3K/AKT/mTOR inhibitors based on preclinical and clinical trials.

A dysregulation of the cell-death mechanism contributes to poor prognosis in lung cancer. New potent chemotherapeutic agents targeting apoptosis-deregulating molecules have been discovered. In this study, 22-(4-pyridinecarbonyl) jorunnamycin A (22-(4′py)-JA), a synthetic derivative of bistetrahydroisoquinolinequinone from the Thai blue sponge, was semisynthesized by the Steglich esterification method, and its pharmacological mechanism in non-small-cell lung cancer (NSCLC) was elucidated by a network pharmacology approach. All predicted targets of 22-(4′py)-JA and genes related to NSCLC were retrieved from drug-target and gene databases. A total of 78 core targets were identified, and their associations were analyzed by STRING and Cytoscape. Gene ontology and KEGG pathway enrichment analyses revealed that molecules in mitogen-activated protein kinase (MAPK) signaling were potential targets of 22-(4′py)-JA in the induction of NSCLC apoptosis. In silico molecular docking analysis displayed a possible interaction of ERK1/2 and MEK1 with 22-(4′py)-JA. In vitro anticancer activity showed that 22-(4′py)-JA has strong cytotoxic and apoptosis-inducing effects in H460, H292 and A549 NSCLC cells. Furthermore, immunoblotting confirmed that 22-(4′py)-JA induced apoptotic cell death in an ERK/MEK/Bcl-2-dependent manner. The present study demonstrated that 22-(4′py)-JA exhibited a potent anticancer effect that could be further developed for clinical application and showed that network pharmacology approaches are a powerful tool to illustrate the molecular pathways of new drugs or compounds.

Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. Despite the fact that various therapeutic compounds have shown potential prevention or treatment, no specific medicine has been developed for the COVID-19 pandemic. Natural products have recently been suggested as a possible treatment option for COVID-19 prevention and treatment. This study focused on the potential of Coriander sativum L. (CSL) against COVID-19 based on network pharmacology approach. Interested candidates of CSL were identified by searching accessible databases for protein–protein interactions with the COVID-19. An additional GO and KEGG pathway analysis was carried out in order to identify the related mechanism of action. In the end, 51 targets were obtained through network pharmacology analysis with EGFR, AR, JAK2, PARP1, and CTSB become the core target. CSL may have favorable effects on COVID-19 through a number of important pathways, according to GO and KEGG pathway analyses. These findings suggest that CSL may prevent and inhibit the several processes related to COVID-19.

Uric acid is the final product of purine metabolism that will be excreted through urine, feces, and sweat. Excessive production of uric acid can cause hyperuricemia, known as gout. The skin of shallots (Allium cepa L.) is one of the household wastes that are very rarely used by the community. Ethanol extract of shallot skin (EESS) was tested for phytochemical screening and anti-hyperuricemia activity using potassium oxonate. Mice were divided into five groups (Allopurinol, Na-CMC, EESS 200 mg/kg BW, 300 mg/kg BW, and 400 mg/kg BW) and uric acid levels were observed at 2-hour intervals for six hours. Phytochemical screening shows that EESS has potential compounds in the treatment of gout. Tests to reduce uric acid levels showed that EESS has better potential than allopurinol at concentrations of 300 mg/kg BW and 400 mg/kg BW after six hours of induction in reducing uric acid levels.

Cancer stands as one of the deadliest diseases afflicting contemporary human societies, encompassing over 100 distinct forms, including oral, salivary glands, oropharynx, nasopharynx, hypopharynx, colorectal, liver, pancreas, lung, skin, breast, cervix, ovary, prostate, kidney, brain, thyroid, and leukemia cancers. At the cellular level, the uncontrolled growth of cancerous cells can disrupt the body's normal functions. Chemotherapy, a widely recognized cancer treatment, utilizes anticancer agents to target specific cancer cell lines effectively. Natural compounds are favored for their compatibility with the body, minimal harm to healthy cells, and easy extraction from natural sources. These natural compounds and their derivatives hold promise for cancer therapy, boasting diverse structural and pharmacological characteristics. Additionally, chemical modifications can enhance their anticancer properties. This review explores the anticancer potential of terpenoids, flavonoids, alkaloids, xanthones, and epoxides, as well as elucidates their molecular mechanisms, such as their antiproliferative, apoptotic, antiangiogenic, and antimetastatic actions. Furthermore, the effect of the functional group on the anticancer activity through the structure-activity relationship will be discussed in detail, supported by molecular docking and molecular dynamic simulations. Combining experimental in vitro and in vivo assays with computational in silico assays significantly helps us understand how we shall fight cancer diseases in the modern era.

The semisynthesis of renieramycin-type derivatives was achieved under mild and facile conditions by attaching a 1,3-dioxole-bridged phenolic moiety onto ring A of the renieramycin structure and adding a 4′-pyridinecarbonyl ester substituent at its C-5 or C-22 position. These were accomplished through a light-induced intramolecular photoredox reaction using blue light (4 W) and Steglich esterification, respectively. Renieramycin M (4), a bis-tetrahydroisoquinolinequinone compound isolated from the Thai blue sponge (Xestospongia sp.), served as the starting material. The cytotoxicity of the 10 natural and semisynthesized renieramycins against non-small-cell lung cancer (NSCLC) cell lines was evaluated. The 5-O-(4′-pyridinecarbonyl) renieramycin T (11) compound exhibited high cytotoxicity with half-maximal inhibitory concentration (IC₅₀) values of 35.27 ± 1.09 and 34.77 ± 2.19 nM against H290 and H460 cells, respectively. Notably, the potency of compound 11 was 2-fold more than that of renieramycin T (7) and equal to those of 4 and doxorubicin. Interestingly, the renieramycin-type derivatives with a hydroxyl group at C-5 and C-22 exhibited weak cytotoxicity. In silico molecular docking and dynamics studies confirmed that the mitogen-activated proteins, kinase 1 and 3 (MAPK1 and MAPK3), are suitable targets for 11. Thus, the structure–cytotoxicity study of renieramycins was extended to facilitate the development of potential anticancer agents for NSCLC cells.