Phytochemical analysis of the dichloromethane:methanol (1∶1) extract of root parts of Prangos pabularia led to the isolation of twelve cytotoxic constituents, viz., 6-hydroxycoumarin (1), 7-hydroxycoumarin (2), heraclenol-glycoside (3), xanthotoxol (4), heraclenol (5), oxypeucedanin hydrate (6), 8-((3,3-dimethyloxiran-2-yl)methyl)-7-methoxy-2H-chromen-2-one (7), oxypeucedanin hydrate monoacetate (8), xanthotoxin (9), 4-((2-hydroxy-3-methylbut-3-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one (10), imperatorin (11) and osthol (12). The isolates were identified using spectral techniques in the light of literature. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity screening of the isolated constituents was carried out against six human cancer cell lines including lung (A549 and NCI-H322), epidermoid carcinoma (A431), melanoma (A375), prostate (PC-3) and Colon (HCT-116) cell lines. Osthol (12) exhibited the highest cytotoxicity with IC₅₀ values of 3.2, 6.2, 10.9, 14.5, 24.8, and 30.2 µM against epidermoid carcinoma (A431), melanoma (A375), lung (NCI-H322), lung (A549), prostate (PC-3) and colon (HCT-116) cell lines respectively. Epidermoid carcinoma cell line A431 was sensitive to most of the compounds followed by lung (A549) cancer cell line. Finally a simple and reliable HPLC method was developed (RP-HPLC-DAD) and validated for the simultaneous quantification of these cytotoxic constituents in Prangos pabularia. The extract was analyzed using a reversed-phase Agilent ZORBAX eclipse plus column C₁₈ (4.6×250 mm, 5 µm) at 250 nm wavelength using a gradient water-methanol solvent system at a flow rate of 0.8 ml/min. The RP-HPLC method is validated in terms of recovery, linearity, accuracy and precision (intra and inter-day validation). This method, because of shorter analysis time, makes it valuable for the commercial quality control of Prangos pabularia extracts and its future pharmaceutical preparations.

Background: BacCancer is regarded as second leading cause of death worldwide. Therefore, there is a high demand for the discovery, development and improvement of novel anti-cancer agents which could efficiently prevent proliferative pathways and clonal expansion of cells. Objective: In view of this, a new series of bioactive scaffolds viz triazoles linked 7-hydroxycoumarin (1) were synthesized using click chemistry approach. Method: All the synthesized compounds were screened for cytotoxicity against a panel of seven different human cancer cell lines viz. Colon (Colo-205 and HCT-116), breast (MCF-7).. lung (NCI-H322 and A549), prostate (PC-3) and skin (A-431) using 3-(4.5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. Results: Among all tested analogs, compound 5, displayed better cytotoxic activity as compared to the parent 7-hydroxycoumarin (1) with IC50 of 5.1, 22.7, 14.3 and 10.2 mu M against breast (MCF-7), lung (NCI- H322), prostate (PC-3) and skin (A-431) cancer cell lines, respectively; the compound 5 was 8-fold more sensitive against MCF-7 than the parent 7-hydroxycoumarin. Moreover, Compound 5 induced both cytotoxic as well as cytostatic effects via induction of apoptosis and G(1) phase arrest, respectively in breast cancer cells (MCF-7). The apoptotic cell population enhanced to 18.8% at 8 mu M of 5 from 9.8% in case of negative control, while G(1) phase arrest increased to 54.4% at 8 mu M compared to negative control of 48.1%. Moreover, Compound 5 also exhibited a remarkable decrease in mitochondrial membrane potential (Lambda Psi m) leading to apoptosis of cancer cells used. Conclusion: The structure-activity relationship study revealed that the derivatives bearing electron-withdrawing substituents were more effective. The present study resulted in identification of the compounds demonstrating broad spectrum cytotoxic activity.

Background: Natural product, osthol has been found to have important biological and pharmacological roles particularly having inhibitory effect on multiple types of cancer. Objective: The unmet needs in cancer therapeutics make its derivatization an important and exciting field of research. Keeping this in view, a whole new series of diverse analogues of osthol (1) were synthesized. Method: All the newly synthesized compounds were made through modification in the lactone ring as well as in the side chain of the osthol molecule and were subjected to anti-proliferative screening through 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) against four different human cancers of diverse origins viz. Colon (Colo-205), lung (A549), Leukemia (THP- 1) and breast (MCF-7) including SV40 transformed normal breast epithelial cell (fR-2). Results: Interestingly, among the tested molecules, most of the analogs displayed better antiproliferative activity than the parent Osthol 1. However, among all the tested analogs, compound 28 exhibited the best results against leukemia (THP1) cell line with IC50 of 5µM.Compound 28 induced potent apoptotic effects and G1 phase arrest in leukemia cancer cells (THP1). The population of apoptotic cells increased from 13.8% in negative control to 26.9% at 8μM concentration of 28. Compound 28 also induced a remarkable decrease in mitochondrial membrane potential (ΛΨm) leading to apoptosis of the cancer cells. Conclusion: A novel series of molecules derived from natural product osthol were synthesized, wherein compound 28 was found to be most effective against leukemia and with 10 fold less toxicity against normal cells. The compound induced cancer inhibition mainly through apoptosis and thus has a potential in cancer therapeutics.

This study introduces an environmentally sustainable approach for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs), via the Biginelli reaction. A heterogeneous catalyst, Heteropolyacid-Clay (HPA-Clay), is developed by immobilizing H5PV2W10O40 on Montmorillonite KSF clay. The catalyst exhibits enhanced stability and catalytic efficiency, confirmed through X-ray powder diffraction and scanning electron microscopy. Utilizing a one-pot multi-component strategy under solvent-free conditions, various aldehydes, urea or thiourea, and ethylacetoacetate generate DHPMs with excellent yields and reduced reaction times. Catalysed by 2 mol% HPA-Clay, the process aligns with green chemistry principles, emphasizing cost-efficiency, environmental sustainability, and recyclability. The catalyst demonstrates consistent activity over multiple cycles, highlighting its potential for advancing Biginelli reactions.