Sepsis can trigger acute respiratory distress syndrome (ARDS), which can lead to a series of physiological changes, modifying the effectiveness of therapy and culminating in death. For all experiments, male Wistar rats (200–250 g) were split into the following groups: control and sepsis-induced by endotoxin lipopolysaccharide (LPS); the control group received only intraperitoneal saline or saline + CEF while the treated groups received ceftriaxone (CEF) (100 mg/kg) IP; previously or not with sepsis induction by LPS (1 mg/kg) IP. We evaluated respiratory mechanics, and alveolar bronchial lavage was collected for nitrite and vascular endothelial growth factor (VEGF) quantification and cell evaluation. For pharmacokinetic evaluation, two groups received ceftriaxone, one already exposed to LPS. Respiratory mechanics shows a decrease in total airway resistance, dissipation of viscous energy, and elastance of lung tissues in all sepsis-induced groups compared to the control group. VEGF and NOx values were higher in sepsis animals compared to the control group, and ceftriaxone was able to reduce both parameters. The pharmacokinetic parameters for ceftriaxone, such as bioavailability, absorption, and terminal half-life, were smaller in the sepsis-induced group than in the control group since clearance was higher in septic animals. Despite the pharmacokinetic changes, ceftriaxone showed a reduction in resistance in the airways. In addition, CEF lowers nitrite levels in the lungs and acts on their adverse effects, reflecting pharmacological therapy of the disease.

A novel hybrid integrating piplartine with a furoxan moiety exhibited a sub-micromolar IC ₅₀ and extraordinary selectivity for PC3 cells, which was associated with its capacity to release NO, generate ROS, induce DNA damage, and trigger apoptosis.

Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed at an advanced stage. The drug arsenal used in systemic therapy for HCC is very limited. Multikinase inhibitors sorafenib (Nexavar^®) and lenvatinib (Lenvima^®) have been used as first-line drugs with modest therapeutic effects. In this scenario, it is imperative to search for new therapeutic strategies for HCC. Herein, the antiproliferative activity of N-acylhydrazone derivatives was evaluated on HCC cells (HepG2 and Hep3B), which were chemically planned on the ALL-993 scaffold, a potent inhibitor of vascular endothelial growth factor 2 (VEGFR2). The substances efficiently reduced the viability of HCC cells, and the LASSBio-2052 derivative was the most effective. Further, we demonstrated that LASSBio-2052 treatment induced FOXM1 downregulation, which compromises the transcriptional activation of genes required for G2/M transition, such as AURKA and AURKB, PLK1, and CDK1. In addition, LASSBio-2052 significantly reduced CCNB1 and CCND1 expression in HCC cells. Our findings indicate that LASSBio-2052 is a promising prototype for further in vivo studies.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. The mortality rate has not reduced despite introducing new therapeutic approaches such as immunotherapy and target-directed therapies. Drug resistance represents a challenge for HCC treatment, resulting in the search for new drug candidates. In the present study, a series of triazole derivatives of guttiferone-A were synthesized and tested against non-small-cell lung cancer (A549), hepatocellular carcinoma (HepG2), and estrogen-positive breast carcinoma (MCF-7) cell lines. Compounds 6, 10, and 12 displayed significant cytotoxic activity on A549 and HepG2 cells, and compound 10 was highly selective toward HepG2 cells. Compound 10 inhibited MAPK/ERK signaling and modulated the expression of critical regulators of the cell cycle progression in HepG2 cells. There was a significant reduction of the cyclins D/E, while p21 was upregulated, indicating that the antiproliferative activity of compound 10 on HepG2 cells, at least in part, is associated with its ability to modulate the expression profile of regulators of G1/S transition. Our findings showed that triazole derivatives of guttiferone-A may be useful as anticancer prototypes and support further in vivo investigation to evaluate the efficiency of compound 10 in suppressing HCC growth and progression.