Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 25, Issue 8, 2025

Tyrosine kinases have emerged as key stimulatory drivers in several cancer-related pathways. This is particularly evident in non-small cell lung cancer with regulating cell growth and apoptosis and so on. Tyrosine kinase inhibitors (TKI) are one breakthrough option that could improve the life quality of cancer patients.

This study aims to find more effective tyrosine kinase inhibitors.

In this study, natural products from TargetMol that may be the potential TKI for lung cancer were screened through structure-based virtual screening and experimental validation. Moreover, the binding between the hit compounds and tyrosine kinase was explored.

From the study findings, Gramicidin and Tannic acid have strong interactions with the four tyrosine kinases (ALK, TRK, MET, and ABL), and this could significantly inhibit the viability of A549 cells in a concentration-dependent manner.

These findings indicated that Gramicidin and Tannic acid might be potential multiple TKI and are promising anticancer agents that call for further study.

As the number of new cancer cases increases every year, there is a necessity to develop new drugs for the treatment of different types of cancers. Plants' resources are considered to be huge reservoirs for therapeutic agents in nature. Among all the medicinal plants, Oroxylum indicum is one of the most widely used medicinal plants in India, China, and Southeast Asian countries. Combinatorial drug treatment, on the other hand, is favored over single drug treatment in order to target multiple biomolecular moieties that help in the growth and development of cancer. Therefore, combinatorial drug treatment using a co-crystal of multiple drugs gives researchers an idea of the development of a new type of drug for targeting multiple targets. In this study, a new co-crystal of chrysin and oroxylin A was isolated from the leaves of O. indicum, and its anticancer properties were studied in cervical cancer cells HeLa.

This study was conducted with the aim of identifying new anticancer compounds from the leaves of Oroxylum indicum and studying the anticancer properties of the isolated compound.

In this study, we elucidated the structure of a new co-crystal compound, which was isolated from the leaf extract of Oroxylum indicum. The apoptosis induction mechanism of the newly discovered co-crystal in HeLa cells was also studied.

A crystal compound from the chloroform extract of leaves of Oroxylum Indicum was isolated by solvent fractionation and chromatographic methods involving HPLC. The molecular structure of the isolated crystal was elucidated by Single Crystal-XRD, FT-IR analysis, and further determined by LC-MS. The antiproliferative activity was carried out using an MTT assay and fluorescence microscopy, and the mechanism of apoptosis was determined using Western blotting techniques.

The novel co-crystal consists of two active pharmaceutical ingredients (APIs) in a 1:1 ratio, i.e., oroxylin A and chrysin. The isolated new co-crystal induced death in HeLa cells with a very low IC50 value of 8.49 µM. It induced caspase-dependent apoptosis in HeLa cells by activation of Caspase-3 through inhibition of ERKs and activation of p38 of MAPK cell signalling pathway.

This study presents the first report on the discovery of a naturally occurring co-crystal of chrysin and oroxylin A and the involvement of ERKs and p38 of MAPK pathways in the induction of apoptosis in HeLa cells by the co-crystal. Our study sheds light on the development of a co-crystal of chrysin and oroxylin A in a specific ratio of 1:1 for combination therapy of the two APIs. The purified co-crystal was found to be more efficient compared to the compounds present individually. Further analysis of the physiochemical properties and molecular mechanisms of the isolated co-crystal in different cancer cells is warranted for its application in therapeutics.

Immunotherapy targeting PD-1/PD-L1 shows significant benefits in lung cancer. Cutaneous immune-related adverse events (irAEs) are frequent, early-developing side effects of ICIs, and their potential role as prognostic markers in non-small cell lung cancer (NSCLC) therapy requires further exploration.

Data of patients with NSCLC treated with camrelizumab Combined with chemotherapy were collected at Xuzhou Medical University from 2019 to 2023. Cutaneous irAEs were monitored using CTCAE v5.0, and therapeutic efficacy was assessed using RECIST 1.1 criteria for ORR and PFS. Multivariable Cox regression analysis identified independent predictors of PFS, and a nomogram was constructed to predict survival outcomes.

Data from 151 patients were analyzed. Significant differences in the objective response rate (ORR, P = 0.016) and progression-free survival (PFS, P < 0.0001) were detected between NSCLC patients, either with cirAEs or not. Besides, PFS was significantly different in NSCLC patients who were subgrouped by the time of first cutaneous irAEs occurrence (P = 0.011), duration of cutaneous irAEs (P = 0.002), grade of cutaneous irAEs (P = 0.002), the number of cutaneous irAEs(P = 0.021). The multivariable analysis also revealed that cirAEs were positively associated with survival outcomes (HR: 0.316, 95% CI, 0.193- 0.519, P<0.001) for PFS. The nomogram was formulated based on the results of multivariate analysis and validated using an internal bootstrap resampling approach, which showed that the nomogram exhibited a sufficient level of discrimination according to the C-index 0.80 (95% CI, 0.748-0.850).

The presence of cirAEs in NSCLC patients treated with camrelizumab combined with chemotherapy is indicative of better treatment efficacy and prognosis. This study supports the utility of cirAEs as biomarkers for predicting the validity of immunotherapy in NSCLC. It proposes a novel, multi-parameter prognostic model to assess patient outcomes more accurately.