Pediatric solid tumors (PSTs) are life-threatening and can lead to high morbidity and mortality rates in children. Developing novel remedies to treat these tumors, such as glioblastoma multiforme and sarcomas, such as osteosarcoma, and rhabdomyosarcoma, is challenging, despite immense attempts with chemotherapeutic or radiotherapeutic interventions. Soy (Glycine max) and kudzu roots (KR) (Pueraria spp.) are well-known phytoestrogenic botanical sources that contain high amounts of naturally occurring isoflavones. In the present study, we investigated the antioxidant and cytotoxic effects of the extracts of KR and soy molasses (SM) against PSTs. The green extraction of isoflavones from KR and SM was performed using natural deep eutectic solvents. The extracts were subsequently analyzed by high-performance liquid chromatography (HPLC)-diode array detector (DAD) coupled with high-resolution (HR) mass spectrometry (MS), which identified 10 isoflavones in KR extracts and 3 isoflavones in the SM extracts. Antioxidant and cytotoxic activities of KR and SM extracts were assessed against glioblastoma multiforme (A-172), osteosarcoma (HOS), and rhabdomyosarcoma (Rd) cancer cell lines. The KR and SM extracts showed satisfactory cytotoxic effects (IC₅₀) against the cancer cell lines tested, particularly against Rd cancer cell lines, in a dose-dependent manner. Antioxidant activity was found to be significantly (p ≤ 0.05) higher in KR than in SM, which was consistent with the results of the cytotoxic activity observed with KR and SM extracts against glioblastoma and osteosarcoma cells. The total flavonoid content and antioxidant activities of the extracts were remarkably attributed to the isoflavone content in the KR and SM extracts. This study provides experimental evidence that HPLC-ESI-HRMS is a suitable analytical approach to identify isoflavones that exhibit potent antioxidant and anticancer potential against tumor cells, and that KR and SM, containing many isoflavones, can be a potential alternative for health care in the food and pharmaceutical industries.

A total of 21 novel xanthone and acridone derivatives were synthesized using the reactions of 1,2,4-triazine derivatives with 1-hydroxy-3-methoxy-10-methylacridone, 1,3-dimethoxy-, and 1,3-dihydroxanthone, followed by optional dihydrotiazine ring aromatization. The synthesized compounds were evaluated for their anticancer activity against colorectal cancer HCT116, glioblastoma A-172, breast cancer Hs578T, and human embryonic kidney HEK-293 tumor cell lines. Five compounds (7a, 7e, 9e, 14a, and 14b) displayed good in vitro antiproliferative activities against these cancer cell lines. Compounds 7a and 7e demonstrated low toxicity for normal human embryonic kidney (HEK-293) cells, which determines the possibility of further development of these compounds as anticancer agents. Annexin V assay demonstrated that compound 7e activates apoptotic mechanisms and inhibits proliferation in glioblastoma cells.

Today, cancer is one of the most widespread and dangerous human diseases with a high mortality rate. Nevertheless, the search and application of new low-toxic and effective drugs, combined with the timely diagnosis of diseases, makes it possible to cure most types of tumors at an early stage. In this work, the range of new polysubstituted 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines was extended. The structure of all the obtained compounds was confirmed by the data of ¹H, ¹³C NMR spectroscopy, IR spectroscopy, and elemental analysis. These compounds were evaluated against human recombinant CK2 using the ADP-GloTM assay. In addition, the IC₅₀ parameters were calculated based on the results of the MTT test against glioblastoma (A-172), embryonic rhabdomyosarcoma (Rd), osteosarcoma (Hos), and human embryonic kidney (Hek-293) cells. Compounds 5f, 5h, and 5k showed a CK2 inhibitory activity close to the reference molecule (staurosporine). The most potential compound in the MTT test was 5m with an IC₅₀ from 13 to 27 µM. Thus, our results demonstrate that 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines are promising for further investigation of their antitumor properties.

Increasing prospective phytochemical investigations and biological activities on Pueraria lobata and Trifolium pratense flowers exhibited their nutritional (food industry) pharmaceutical (anticancer, anti-inflammatory, anti-microbial, etc.) potentials. Previous studies paid great attention to the screening of isoflavones profile from phytochemicals. This study, in contrast, aimed at identifying the flavonoids from Pueraria lobata flowers or kudzu flower (KF) and Trifolium pratense flowers or red clover (RC) flowers and determining their cytotoxic activities on normal; (HEK-293) and cancer cell lines; human glioblastoma (A-172), osteosarcoma (HOS), embryonic rhabdomyosarcoma (Rd), lung carcinoma (A-549) and liver carcinoma (HepG2). The phytochemical screening using a high-performance liquid chromatography-diode array detector coupled with quadrupole time-of-flight mass spectrometry (HPLC-DAD-Q-TOF/MS) showed that 15 flavonoids, including isoflavones, flavones, flavonols, and flavanones, were identified in KF and 8 flavonoids, including isoflavones and flavonols, were found in RC. Nevertheless, the majority of flavonoid chemical constituents in KF or RC were found to be isoflavones (66.6%) and (62.5%), respectively. HPLC-DAD analysis following eco-friendly extraction of phytochemicals showed that KF contains mainly daidzein and genistein, while RC contains primarily formononetin and biochanin A. Cytotoxic activities evaluated according to IC₅₀ values exhibited the most pronounced dose-dependent antiproliferative effect of KF and RC extracts were against HOS and Rd cancer cell lines, respectively. Accordingly, the morphological observation carried out using acridine orange/ethidium bromide and Giemsa stains revealed apoptotic activities and cell death in HOS and Rd cell lines when subjected to KF or RC extracts. Cytotoxic activities and apoptotic changes were pronounced among all cancer cell lines except for the control cells (HEK-293). Additionally, various polyphenols and flavonoids were identified and quantified in KF and RC extracts and exhibited potent radical scavenging activities. Overall, this study suggests that KF and RC could be valuable edible sources of flavonoids. The comprehensive flavonoid profiles for KF and RC may explain their remarkable biological activities and contribution to inducing antioxidant and cytotoxic activities against cancer cell lines.

We have designed and synthesized a series of bioinspired pyrano[2,3-f]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and preserving their bioactive properties. Three directions for the synthesis were explored: reaction of 5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one with (i) 1,2,4-triazines, (ii) sulfonylation followed by Suzuki cross-coupling with (het)aryl boronic acids, and (iii) aminomethylation by Mannich reaction. Antiviral assay of the synthesized compounds showed that compound 4 has moderate activity against HIV-1 on enzymes and poor activity on the cell model. A molecular docking study demonstrates a good correlation between in silico and in vitro HIV-1 reverse transcriptase (RT) activity of the compounds when docked to the nonnucleoside RT inhibitor binding site, and alternative binding modes of the considered analogs of Calanolide A were established.