Cancer is one of the biggest challenges for health concerns in the world. There are so many drugs available, but they have a lack of specificity, poor safety, side effects, and the development of resistance. Therefore, there is an urgent need for much safer and more targeted anticancer treatments. Nitrogen-containing heterocycles play an important role in the development of drugs. Recently, imidazole and phenothiazine rings are well known for their antiproliferative and anticancer activities. This study employs the molecular hybridisation method to link these bioactive scaffolds and develop novel N-substituted imidazole-phenothiazine (N-IPTZ) hybrids. All the synthesised hybrids were characterised by using analytical techniques such as ¹H-NMR,¹³C-NMR, mass spectrum, and FT-IR. Furthermore, the DFT analysis under the B3LYP/6-311G(d, p) level in gas phase to optimise and correlate the structures of the synthesised hybrids was also performed. The optimised structure was used to determine the energies of frontier molecular orbitals (HOMO-LUMO), quantum chemical descriptors (QCD), and molecular electrostatic potentials (MEP). Additionally, in silico approaches such as ADMET, BOILED-Egg, and bioactivity radar were also performed to evaluate the oral bioavailability of the synthesised hybrids. Molecular docking and MD simulation studies were also conducted to assess the interaction profile of the synthesised hybrids with cancer target receptors like EGFR, IGF, VEGFR1, VEGFR2, and PARP-2. It was found through docking studies that the synthesised N-IPTZ(a-c) hybrids might interact with amino acids such as GLY695, SER696, GLY697, ALA698, PHE699, LYS721, GLY772, CYS773, THR766, GLN767, LEU768, MET769, ARG817, ASN818, and THR830. Additionally, it reveals hydrogen bonding with ASP831, with binding energies of − 7.23, − 6.11, and − 5.93 kcal/mol. Moreover, all the synthesised hybrids were also analysed for their anti-cancer activity against the human liver cancer cell line (HepG2) by MTT assay. Obtained results revealed that N-IPTZ(c) exhibited anticancer activity with an IC₅₀ value of 35.3 µg/mL.

Due to the lack of approved vaccines against Cutaneous Leishmaniasis (CL), chemotherapy is the only treatment option. Presently, none of the current CL drugs have high levels of efficacy and safety profiles. Thus, the development of new and safer drugs is urgently needed. Drug repurposing can be used for the development of new therapeutic activities. Phosphomannomutase (PMM) has become highlighted as a potential drug target due to its important role in the biosynthesis of glycoconjugates which is essential for parasite virulence. To identify new promising lead molecules, we have performed virtual screening of 8,500 drugs and selected 46 drugs for docking simulation through the Glide module of Schrodinger software. The saquinavir and grazoprevir showed the highest binding affinity (-10.144 and -10.131 kcal/mole). To find the stability of both complexes, molecular dynamics (MD) simulation were performed at 100ns. The grazoprevir-2i54 and saquinavir-2i54 complexes showed good stability in the active site of the receptor. It could be an alternative drug for the treatment of CL.

Isatin-based chalcone derivatives (3a-b) have garnered significant attention due to their versatile biological activities and potential therapeutic applications. Our research goes to the development of new small molecules of isatin-containing druglikeness using the Claisen Schmidt reaction. Actually, analytical techniques like FT-IR, 1H, 13C NMR, and HRMS were deployed for the reporting to successfully characterize. As a preliminary investigation, synthesized compounds were passed through the computed strategy to find out the druglikeness properties. Further, the in-vitro analysis was conducted for synthesized compounds against representative bacteria B. pumilis (MTCC 160), B. cerius (MTCC1305), E. coli (ATCC 25923) and K. pneumoniae (NCTC418) obtained from NCIM, Pune (INDIA). n this study, the synthesized compound 3a, showed more significant activity against E. coli (ATCC 25923) at 93.5 µg/ml .While other strains like B. cerius (MTCC1305), Klebsiella pneumonia (NCTC418) and B. Pumilis (MTCC 160) at 187.2μg/ml, 156.5μg/ml and 156.25 μg/ml. This study emphasizes the relevance of combining synthetic chemistry and computational approaches to speed up drug development procedures using isatin-based chalcone derivatives.

Phenothiazine and its N-substituted derivatives are pivotal in heterocyclic chemistry, and serves as potential building blocks in chemical and pharmaceutical sciences. Over the past decade, extensive research has focused on the medicinal potentials of these compounds, exploring their anticancer, analgesic, anti-tumor, anti-inflammatory, and antibacterial properties. Due to their distinctive chemical compositions, phenothiazine and its N-substituted derivatives have facilitated the development of novel substitutions. This paper reviews recent advancements in the synthesis of phenothiazine and its N-substituted derivatives, with an emphasis on their potential biological roles. Numerous investigations have identified various types of phenothiazine and its N-substituted derivatives that exhibit compelling biological characteristics. It discusses the impact of different functional groups on phenothiazine at the N-substitution, specifically Cl, CF₃, OH, N(C₂H₅)₂, and (CH₂)₅CH₃. Furthermore, the relationship between the biological activities and the structural characteristics of the compounds is examined, identifying the chemical groups and structural alterations that enhance bioactivity, reduce toxicity, and improve handling.

Background/Objectives: The current need for new antibacterial compounds that target non-classical pathways is highlighted by the emergence of multidrug-resistant Klebsiella pneumoniae. In the development of antibiotics, DNA adenine methyltransferase (Dam), a key regulator of bacterial gene expression and pathogenicity, is still underutilized. Epoxy-functionalized analogues of isatin derivatives have not been adequately investigated for their antibacterial activity, particularly as Dam inhibitors. In the pursuit of antimicrobial agents, this study synthesized an epoxy-functionalized isatin derivative (L3) using a one-pot reaction. The compound was characterized using FT-IR, ¹H-NMR, ¹³C-NMR, HR-MS, and UV–Vis spectroscopy. Methods: In silico evaluation performed by using ADMETlab3 and SwissADME. While molecular docking studies were achieved by AutoDock and Vina to find L3’s interaction with potential antibacterial target (Dam protein in K. pneumoniae). In addition, the antibacterial potential of L3 was evaluated using minimum inhibitory concentration (MIC) assays against Bacillus cereus, Bacillus pumilus, Escherichia coli, and K. pneumoniae. Results: Among these, L3 exhibited potential inhibitory activity against K. pneumoniae, with a MIC value of 93.75 μg/mL. In silico evaluations confirmed L3’s favorable drug-like properties, including potential oral bioavailability, blood–brain barrier (BBB) permeability, and low plasma protein binding (PPB). The compound satisfied Lipinski’s and other drug-likeness rules as well as getting a quantitative estimate of drug-likeness (QED) score of 0.52. Here, a homology model of Dam protein in K. pneumoniae was generated using the SWISS-MODEL server and validated using computational tools. Targeted docking analysis revealed that L3 exhibited significant potential binding affinity against Dam protein, with binding energies of −6.4 kcal/mol and −4.85 kcal/mol, as determined by Vina and AutoDock, respectively. The associated inhibition constant was calculated as 280.35 µM. Further interaction analysis identified the formation of hydrogen bonds with TRP7 and PHE32, along with Van der Waals’ interactions involving GLY9, ASP51, and ASP179. Conclusions: These findings highlight L3 as a promising scaffold for antimicrobial drug development, particularly in targeting Dam protein in K. pneumoniae. Furthermore, the ADMET profiling and physicochemical properties of L3 support its potential as a drug-like candidate.