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Item An in silico approach to identify novel and potential Akt1 (protein kinase B-alpha) inhibitors as anticancer drugs(Springer Nature, 2025) Etikyala, U.; Reddyrajula, R.; Vani, T.; Kuchana, V.; Udayakumar, U.; Vijjulatha, V.Akt1 (protein kinase B) has become a major focus of attention due to its significant functionality in a variety of cellular processes and the inhibition of Akt1 could lead to a decrease in tumour growth effectively in cancer cells. In the present work, we discovered a set of novel Akt1 inhibitors by using multiple computational techniques, i.e. pharmacophore-based virtual screening, molecular docking, binding free energy calculations, and ADME properties. A five-point pharmacophore hypothesis was implemented and validated with AADRR38. The obtained R2 and Q2 values are in the acceptable region with the values of 0.90 and 0.64, respectively. The generated pharmacophore model was employed for virtual screening to find out the potential Akt1 inhibitors. Further, the selected hits were subjected to molecular docking, binding free energy analysis, and refined using ADME properties. Also, we designed a series of 6-methoxybenzo[b]oxazole analogues by comprising the structural characteristics of the hits acquired from the database. Molecules D1–D10 were found to have strong binding interactions and higher binding free energy values. In addition, Molecular dynamic simulation was performed to understand the conformational changes of protein–ligand complex. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024.Item Exploring Indole-1,3,4-Thiadiazole Schiff Base Derivatives as Anticancer Agents: Design, Synthesis, In Vitro and In Silico Evaluation(John Wiley and Sons Ltd, 2025) Etikyala, U.; Reddyrajula, R.; Udayakumar, U.; Kokku, P.; Vijjulatha, V.Cancer remains a major global health challenge, with resistance to existing therapeutic regimens underscoring the development of novel agents with improved efficacy and reduced toxicity. The indole and 1,3,4-thiadiazole scaffolds are distinguished for their broad-spectrum bioactivities, including anticancer properties. In this study, the synthesis and biological evaluation of a new series of indole-1,3,4-thiadiazole Schiff bases (U1-U31) designed to enhance anticancer efficacy is explored. In vitro evaluation demonstrates potent and selective cytotoxicity of several compounds, particularly U19 and U24, against multiple cancer cell lines, with minimal toxicity to normal cells. Molecular docking and density functional theory studies demonstrate that these hybrid compounds effectively occupy the ATP-binding sites of Pi3K and Akt proteins, exhibiting notable binding interactions comparable to the respective standard inhibitors. In addition, molecular dynamics simulation is performed to understand the conformational changes of the protein–ligand complex. Overall, the findings indicate that these novel indole-1,3,4-thiadiazole derivatives have selective inhibitory potency, making them promising leads for further anticancer drug development. © 2025 Wiley-VCH GmbH.