Conventional drug discovery process is associated with high costs, lengthy development timelines, and high failure rates mainly for complex multifactorial diseases. These challenges highlight the existing need for various innovative discovery strategies. Natural product continues to play an important role in discovery of drugs, with natural compounds and their derivatives accounting for approximately one-third of all small-molecule drugs that were approved from 1981 to 2019. Currently, computational and systems-based approaches are being increasingly incorporated in various steps of herbal-drug discovery. These approaches include molecular docking, virtual screening, quantitative structure-activity relationship (QSAR) modelling, network pharmacology, and bioactivity prediction using machine learning. Other emerging technologies such as genome editing and synthetic biology also provide additional opportunities to access and optimize valuable natural-product metabolites. Together, these tools can aid in identifying candidate molecules, elucidate potential mechanisms, and formulation development, although all of it requires experimental validation. Herbal medicines can modulate multiple molecular targets, hence can be advantageous for complex diseases. Analytical techniques such as hyphenated spectroscopy and metabolomics can further contribute to standardization and quality control. Nanocarrier systems and pharmacogenomic approaches can increase bioavailability and support more personalized therapeutic strategies. This review highlights integrated approaches for improving discovery, validation, and herbal therapeutic development. The combination of traditional knowledge with computational and analytical approaches provides a practical framework for herbal product-based drug discovery. Continued progress will depend on standardization, reproducible methodologies, and robust clinical evidence.
Akhil Nair, Sinchana Suvarna, Shruthika Karkera et al.· Beni-Suef University Journal...· 0 citations
As the field of anticancer drug development is constantly changing, combining synthetic lethality with epigenetic modifiers opens up new possibilities for targets that fall outside the traditional drug target range. Enzymes involved in DNA methylation and histone modification are examples of epigenetic modifiers that promote gene expression without altering the DNA sequence of the gene. These mechanisms play a key role in carcinogenesis when they are altered, as they downregulate tumor suppressor genes and overexpress oncogenic pathways. Synthetic lethality is a phenomenon in which simultaneous mutations or perturbations of two genes result in cell death, but alterations to one gene alone do not cause cell death. It was first observed in genetic research conducted on model organisms, such as fruit flies and fungi. The most well-known example of this idea from the perspective of cancer treatment is PARP inhibitors, which are effective in tumors with BRCA1/2 mutations, where further failure of DNA repair results in cell sensitization. Building on the concept of synthetic lethality, current research focuses on exploiting epigenetic flaws that are common in cancer cells. For example, when chromatin remodelers or methyltransferases cease to function, malignant cells undergo genetic rewiring, rendering them vulnerable to treatment. Recent research has produced some striking examples of synthetic-lethal drug interactions and biomarkers used in metagenomics for personalized medicine by targeting the secondary pathways used by cancer cells as a result of primary loss-of-function mutations, which selectively kill cancer cells while sparing healthy cells. The discovery of actionable epigenetic dependencies and overcoming tumor heterogeneity remain the largest challenges in translating these fascinating scientific discoveries to the clinic. The convergence of epigenetic modulators with synthetic-lethality-based therapeutic architectures is poised to define a transformative paradigm in precision oncology. By orchestrating multilayered perturbations across chromatin-regulatory networks, DNA damage-response pathways, and context-specific vulnerability nodes, this integrative strategy surpasses the limitations of conventional target-centric pharmacology and enables mechanistically rational, synergistic antitumor interventions.
Venkatesh Kamath, Vasudev Pai, Bhavana Bhat et al.· Current Topics in Medicinal...· 0 citations
