Exploring MTH1 inhibitory potential of Thymoquinone and Baicalin for therapeutic targeting of breast cancer.

Cancers frequently have increased ROS levels due to disrupted redox balance, leading to oxidative DNA and protein damage, mutations, and apoptosis. The MTH1 protein plays a crucial role by sanitizing the oxidized dNTP pools. Hence, cancer cells rely on MTH1 to prevent the integration of oxidized dNTPs into DNA, preventing DNA damage and allowing cancer cell proliferation. We have discovered Thymoquinone (TQ) and Baicalin (BC) as inhibitors of MTH1 using combined docking and MD simulation approaches complemented by experimental validations via assessing binding affinity and enzyme inhibition. Docking and MD simulations studies revealed an efficient binding of TQ and BC to the active site pocket of the MTH1, and the resultant complexes are appreciably stable. Fluorescence measurements estimated a strong binding affinity of TQ and BC with Ka 3.4 ×106 and 1.0 ×105, respectively. Treating breast cancer cells with TQ and BC significantly inhibited the growth and proliferation (IC50 values 28.3 µM and 34.8 µM) and induced apoptosis. TQ and BC increased the ROS production in MCF7 cells, imposing substantial oxidative stress on cancer cells and leading to cell death. Finally, TQ and BC are proven strong MTH1 inhibitors, offering promising prospects for anti-cancer therapy.

Analysis of genetic structure and interrelationships in lentil species using morphological and SSR markers.

Genetic structure and relationships of 130 lentil accessions belonging to six taxa were analysed. For this purpose, seven morphological traits and 31 polymorphic simple sequence repeat (SSR) primers were used for this purpose. Morphological traits grouped lentil accessions into five main clusters. SSR primers collectively amplified 139 polymorphic alleles in a range of 2-10 with an average of 4.48 alleles. The size of amplified alleles varied from 50 to 650 bp. Polymorphism information content (PIC) ranged from 0.02 to 0.85 with an average of 0.46. Neighbour-joining tree grouped accessions broadly according to their taxonomic ranks, except L. culinaris ssp. odemensis. Analysis of molecular variance (AMOVA) revealed that a major portion (82.0%) of genetic variance resided within species, while only 18% resided among species. Bayesian model-based STRUCTURE analysis assigned all accessions into five clusters and showed some admixture within individuals. Cluster analysis showed that cultivated Lens accessions of Ethiopian origin clustered separately, from other cultivated accessions indicating its distinct lineage. Among the analysed lentil species, L. culinaris ssp. odemensis seemed to have conserved genetic background and needs revision of its taxonomic status. Results of present study provide important information on genetic diversity and relationships among different wild and cultivated taxa of lentil. Thus, these results can be useful in designing breeding strategies for future improvement and taxonomic implications in lentil.