Computational Design of Novel Anticancer Agents for Lung Cancer: A Molecular Docking and ADMET Analysis

EGFR-Targeted Amino Quinoxaline Derivatives as Potential Anticancer Interventions: In Silico Design and in Vitro Evaluations

The Epidermal Growth Factor Receptor (EGFR) remains validated therapeutic goalfor Breast Cancer, especially because of its function in signalling pathways that promote tumor development and viability. In the current investigation, a series of newly designed amino quinoxaline derivatives (QN1–QN10) were investigated for their potential EGFR inhibitory and anticancer activities using an integrated in silico and in vitro approach. Molecular docking studies were carried out using Schrödinger Maestro to rate the binding kineticsof the designed compounds with the EGFR tyrosine kinase domain (PDB ID: 4HJO), employing erlotinib as the reference standard. The docking protocol was validated by redockingerlotinib into the active site, confirming the reliability of the methodology. Glide extra-precision (XP) docking revealed favourable binding orientations of selected derivatives within the EGFR catalytic pocket. The cytotoxicity of selected compounds (QN2, QN4, and QN8) was further calculated through MTT assay for human breast cancer cell line MCF-7. The results proved that the cell longevity was decreased in a concentration-dependent way, with erlotinib exhibiting the greatest potency (LC50 = 18.47 µg/mL). Among the synthesized derivatives, QN4 showed relatively higher activity (LC50 = 121.52 µg/mL) than QN2 and QN8.Statistical analysis proved the relevance of the cytotoxic effects observed (p < 0.0001). Overall, the combined computational and biological findings suggest that amino quinoxaline scaffolds indicate potential avenues for enhanced optimization as EGFR-targeted anticancer drugs.

Mechanism and Molecular Target of Substituted Triazoles: A Therapeutic Strategy in Anticancer Drug Discovery.

Cancer remains a leading cause of mortality worldwide, necessitating the continuous discovery and development of novel therapeutic agents with improved efficacy and reduced toxicity. Heterocyclic compounds are privileged scaffolds in medicinal chemistry, and among them, the triazole ring system (1,2,3-triazoles and 1,2,4-triazoles) has emerged as a highly versatile and promising pharmacophore for anti-cancer drug discovery. This review is an attempt to bridge the gap between synthetic structural biology and translational oncology by systematically connecting the structure- activity relationships of novel triazole hybrids targeting Aromatase, VEGFR-2, IDO1, and Carbonic Anhydrase. We present a comprehensive overview of the recent advancements in the design, structure-activity relationships, and biological evaluation of triazole derivatives as potent anticancer agents. Triazoles are known to play an important role in modulating key oncogenic pathways (such as apoptosis induction, cell cycle arrest, angiogenesis inhibition, and metastasis suppression) by binding to various pharmacological targets. Here, we critically present the spatial configuration, such as the "tail approach" needed for carbonic anhydrase inhibition and the very specific heme-iron distances of the IDO1 pathway that govern the therapeutic promise. Clinical progress, toxicity, bioavailability, and resistance challenges have also been addressed. This review underscores the significance of triazole derivatives as multifunctional anticancer agents and provides insights into future directions for their development as targeted and potent chemotherapeutic agents. Although triazole derivatives are widely recognized as versatile, drug-like moieties, a critical research gap persists in understanding minor structural or electronic modifications near the triazole ring system to make the molecule target-specific and prevent liabilities due to non-selectivity.

Quinoline clubbed triazole hybrids as VEGFR-2 targeted anticancer agents: synthesis, molecular modeling, and biological evaluation

In silico investigation of novel isatin derivatives as potential multi-target anticancer agents targeting VEGFR-2, EGFR, and caspase-6.

This study highlights the usefulness of computational approaches in the discovery of novel isatin-based multi-target lead candidates for cancer therapy and suggests that compound 4 represents a promising lead for further investigation.

Structure-Based In Silico Screening of PubChem Compounds for Potential Anti-Inflammatory and Anticancer Targets

C25, the pyrazolin derivative represents a novel multi-target ligand with potential applications as an anti-inflammatory, analgesic, and anti-neoplastic agent and highlights its promise as a lead scaffold for future drug development.

Design, synthesis, molecular docking, ADMET and anticancer evaluation of novel pyridine/thiazole hybrids as dual VEGFR-2 and EGFR kinase inhibitors.

Here, we highlight the synthesis of a number of novel pyridine/thiazole hybrids 1 to 6a,b and their screening as possible anticancer drugs through dual targeting of VEGFR-2 and EGFR. The novel compounds were created in accordance with the structural specifications of the target receptors. The MTT assay was used to assess the compounds' cytotoxicity against the cancer cell lines HepG2, MCF-7, HCT116, and A549. With IC50 values of 6.50, 7.00, 5.55, and 6.85 μM against HepG2, MCF-7, A549, and HCT116 cell lines, respectively, compound 5b demonstrated the strongest anticancer activity. Although it was less effective than sorafenib against the studied cell lines, it was more effective than erlotinib against HepG2, MCF-7, and HCT116, while it was less effective against A549. The six potent compounds 4a, 4b, 4c, 5a, 5b, 6a, and 6b were assessed for their toxic effects on VERO normal cell lines to determine cytotoxicity levels. Results across all studies indicated that every synthesized compound demonstrated minimal toxicity toward VERO normal cells, with IC50 values ranging between 47.60 and 52.22 μM. Additionally, molecular modeling studies were used to investigate how well the novel derivatives could interact with EGFR and VEGFR-2 receptors. Furthermore, the compounds underwent additional testing to measure their capacity to inhibit both EGFRT790M and VEGFR-2. Compounds 5b, 4b, 4c, and 6b demonstrated excellent inhibitory potency against VEGFR-2, exhibiting IC50 values of 0.95, 1.00, 1.15, and 1.35 μM, respectively. Also, compounds 5b, 4c, 4b, and 6b inhibited EGFRWT activity with IC50 = 0.24, 0.30, 0.37 and 0.40 μM respectively. Similarly, these same compounds displayed superior inhibitory effects on EGFRT790M, with corresponding IC50 values of 0.26, 0.36, 0.44, and 0.50 μM, respectively. Notably, derivatives 5b, 4b, and 4c exhibited good in silico ADMET predictions.