New target molecules, namely, 2-phenylamino-4-phenoxyquinoline derivatives, were designed using a molecular hybridization approach, which was accomplished by fusing the pharmacophore structures of three currently available drugs: nevirapine, efavirenz, and rilpivirine. The discovery of disubstituted quinoline indicated that the pyridinylamino substituent at the 2-position of quinoline plays an important role in its inhibitory activity against HIV-1 RT. The highly potent HIV-1 RT inhibitors, namely, 4-(2′,6′-dimethyl-4′-formylphenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6b) and 4-(2′,6′-dimethyl-4′-cyanophenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6d) exhibited half-maximal inhibitory concentrations (IC50) of 1.93 and 1.22 µM, respectively, which are similar to that of nevirapine (IC50 = 1.05 µM). The molecular docking results for these two compounds showed that both compounds interacted with Lys101, His235, and Pro236 residues through hydrogen bonding and interacted with Tyr188, Trp229, and Tyr318 residues through π–π stacking in HIV-1 RT. Interestingly, 6b was highly cytotoxic against MOLT-3 (acute lymphoblastic leukemia), HeLA (cervical carcinoma), and HL-60 (promyeloblast) cells with IC50 values of 12.7 ± 1.1, 25.7 ± 0.8, and 20.5 ± 2.1 µM, respectively. However, 6b and 6d had very low and no cytotoxicity, respectively, to-ward normal embryonic lung (MRC-5) cells. Therefore, the synthesis and biological evaluation of 2-phenylamino-4-phenoxyquinoline derivatives can serve as an excellent basis for the development of highly effective anti-HIV-1 and anticancer agents in the near future.

Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new therapeutic targets for CSCs is critical. Dinactin is a natural secondary metabolite produced by microorganisms. Recently, dinactin has been revealed as a promising antitumor antibiotic via various mechanisms. However, the evidence relating to cell cycle progression regulation is constrained, and effects on cancer stemness have not been elucidated. Therefore, the aim of this study is to evaluate the new function of dinactin in anti-NSCLC proliferation, focusing on cell cycle progression and cancer stemness properties in Lu99 and A549 cells. Flow cytometry and immunoblotting analyses revealed that 0.1–1 µM of dinactin suppresses cell growth through induction of the G₀/G₁ phase associated with down-regulation of cyclins A, B, and D3, and cdk2 protein expression. The tumor-sphere forming capacity was used to assess the effect of dinactin on the cancer stemness potential in NSCLC cells. At a concentration of 1 nM, dinactin reduced both the number and size of the tumor-spheres. The quantitative RT-PCR analyses indicated that dinactin suppressed sphere formation by significantly reducing expression of CSC markers (i.e., ALDH1A1, Nanog, Oct4, and Sox2) in Lu99 cells. Consequently, dinactin could be a promising strategy for NSCLC therapy targeting CSCs.

The increasing demand for natural therapeutics has driven interest in plant-derived essential oils as potential alternatives to synthetic drugs for managing infectious and chronic diseases. Plectranthus amboinicus is a traditional medicinal plant known for its diverse therapeutic uses, particularly in Asian and African folk medicine. In this study, the chemical composition and biological activities of P. amboinicus essential oil (PAEO), derived from plants grown in Phetchabun, Thailand, were investigated. Gas chromatography–mass spectrometry (GC–MS) analysis identified 142 volatile compounds, with shyobunol (9.1%), germacrene D (8.3%), α-cadinol (7.7%), and carvacrol (7.5%) being the predominant constituents. Antibacterial testing revealed that PAEO exhibited moderate to strong bactericidal activity against Escherichia coli, Salmonella Typhimurium, and Shigella flexneri, with minimum inhibitory concentrations (MIC) ranging from 1 to 2 mg/mL. Time-kill kinetics assays demonstrated a rapid bactericidal effect, whereas post-antibiotic effect (PAE) analysis showed prolonged suppression of bacterial regrowth compared with standard antibiotics. Scanning electron microscopy (SEM) and biochemical studies confirmed that PAEO disrupts bacterial cell membranes, leading to the leakage of nucleic acids and proteins. In addition, PAEO significantly inhibited the activity of angiotensin-converting enzyme 1 (ACE1) in vitro in a dose-dependent manner, achieving over 70% inhibition at 1 mg/mL, with a median inhibitory concentration (IC₅₀) of approximately 0.51 mg/mL. These results highlight the potential of PAEO as a multifunctional agent for the treatment of microbial infections and hypertension warranting further preclinical and clinical investigation.