Steroidal hydrazones as antimicrobial agents: biological evaluation and molecular docking studies

Synthesis of new 1,2,3-triazole linked benzimidazolidinone: Single crystal X-ray structure, biological activities evaluation and molecular docking studies

Biological evaluation, molecular docking and DFT studies of charge transfer complexes of quinaldic acid with heterocyclic carboxylic acid

In search of new active molecules, a small focused library of tetrazoloquinoline-based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be exhibiting promising antimicrobial and antioxidant activity characterized by their lower minimum inhibitory concentration values. All the synthesized compounds exhibited excellent antibacterial activity against Gram negative bacteria E. coli and F. devorans and antifungal activity against C. albicans and A. niger. Further, these compounds were tested for their antitubercular activity against dormant MTB H37Ra and dormant M. bovis BCG using XRMA assay protocol and showed no significant activity. Also, the synthesized compounds were found to have potential antioxidant activity with IC50 range = 12.48–50.20 μg/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against the active site of fungal C. albicans enzyme P450 cytochrome lanosterol 14α-demethylase, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole-incorporated tetrazoloquinolines may possess the ideal structural requirements for further development of novel therapeutic agents.

Experimental and DFT studies of 2-methyl-quinoxaline and its silver (I) complex: Non-covalent interaction analysis, antimicrobial activity and molecular docking study

Infectious diseases are still one of the leading causes of death and disability in human society. Synthetic antimicrobial agents have recently emerged as promising candidates against drug‐resistant pathogens. Here we described an efficient procedure for synthesis of aryloxyalkyl theophylline analouges as novel antimicrobial agents. Fourtheen new compounds were synthesized ( 5 a – 5 n ) and their chemical structures were approved by different spectroscopic methods. The synthesized compounds were screened for their antimicrobial activities by broth micro dilution method as recommended by Clinical and Laboratory Standards Institute (CLSI). Molecular docking studies were also performed to forecast their binding modes against cytochrome P 450 lanosterol 14α‐demethylase as a main target. The results represented appropriate correlation between molecular docking and antimicrobial activity of the compounds. Based on biological results and in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions, compound 5 g can be considered as an ideal antimicrobial agent for the future studies.

Design, synthesis, biological evaluation, molecular docking and QSAR studies of 2,4-dimethylacridones as anticancer agents

N-benzylimidazoles as potential antimicrobial and antibiofilm agents – syntheses, bioactivity and molecular docking studies

This study aims to synthesize antimicrobial agents and their molecular docking, and DFT studies of benzothiazole-imidazolone scaffolds. Benzothiazole and imidazolone analogues are of interest due to their potential activity against microbial infections. In search of suitable antimicrobial compounds, we report here the synthesis, characterization, and biological activities of benzothiazole and imidazolone analogues (4a-l). The benzothiazole clubbed imidazolone motifs were synthesized, characterized, and screened for their antimicrobial activity. Molecular docking was carried out for the development of antimicrobial agents based on the results of biological activity obtained. We have synthesized a new series of benzothiazole-clubbed imidazolone hybrids by using multi-step reactions in the search for antimicrobial agents (4a-l). The structures were determined by 1H NMR, 13C NMR, IR, and mass spectroscopy techniques. Moreover, synthesized compounds were evaluated for their antimicrobial activity by using a Serial Broth Dilution method. In addition, molecular electrostatic potential, geometric optimization, and molecular reactivity analyses (HOMO-LUMO) of 4c, which is one of the compounds with the highest antibacterial activity, were performed. The in vitro antimicrobial activity was evaluated against pathogenic strains. Among them, compounds 4c showed the most potent biological activity against Gram-negative bacteria, E. coli with MIC values of 50 μg/mL, and compound 4c active against A. clavatus with MIC values of 100 μg/mL. Active compound 4c HUMO-LUMO energies, molecular electrostatic potential analysis, and geometric optimization parameters were calculated with a 6-31G ** base set using DFT/B3LYP theory, and the results were displayed. Molecular docking studies were performed on E. coli DNA Gyrase B to understand the binding interaction of compound 4c, and it was observed that compound 4c interacted with Arg76 amino acid of the active site through hydrophobic interaction. Benzothiazole-clubbed imidazolone hybrids (4a-l) indicated promising antimicrobial activity. Among them, compounds 4b (MIC=50 μg/mL C. albicans), 4c (MIC=50 μg/mL, E. coli), 4e (MIC= 100 μg/mL, A. niger), and 4g (MIC= 50 μg/mL, S. pyogenes) with electronwithdrawing bromo, chloro, and fluoro group at the para position of the phenyl ring on benzothiazole-imidazolone hybrids indicated remarkable potency compared to the standard drug. The geometric optimization, molecular reactivity, and MESP analyses of 4c were calculated with the B3LYP/6-31G ** base set and ΔE = ELUMO-EHOMO, which was found to be - 0.12096 eV. In addition, the binding affinity scores correlated well with the in vitro antimicrobial activity (4c), while their binding modes proposed the involvement of steric, electrostatic, and hydrogen- bonding interactions with the active site.

Decision letter for "Synthesis and characterization of novel <i>N</i>-(2-(pyrazin-2-yl-oxy)ethyl)-4-(trifluoromethoxy)benzamide scaffolds, and biological evaluation and molecular docking studies"

Review for "Synthesis and characterization of novel <i>N</i>-(2-(pyrazin-2-yl-oxy)ethyl)-4-(trifluoromethoxy)benzamide scaffolds, and biological evaluation and molecular docking studies"

Three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking studies were carried out to explore the binding of 73 inhibitors to dipeptidyl peptidase IV (DPP-IV), and to construct highly predictive 3D-QSAR models using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The negative logarithm of IC(50) (pIC(50)) was used as the biological activity in the 3D-QSAR study. The CoMFA model was developed by steric and electrostatic field methods, and leave-one-out cross-validated partial least squares analysis yielded a cross-validated value (r(2)(cv)) of 0.759. Three CoMSIA models developed by different combinations of steric, electrostatic, hydrophobic and hydrogen-bond fields yielded significant r(2)(cv) values of 0.750, 0.708 and 0.694, respectively. The CoMFA and CoMSIA models were validated by a structurally diversified test set of 18 compounds. All of the test compounds were predicted accurately using these models. The mean and standard deviation of prediction errors were within 0.33 and 0.26 for all models. Analysis of CoMFA and CoMSIA contour maps helped identify the structural requirements of inhibitors, with implications for the design of the next generation of DPP-IV inhibitors for the treatment of type 2 diabetes.

This study focuses on the search for new effective synthetic antimicrobial compounds as a tool against the widespread presence of microorganisms resistant to existing drugs. Five derivatives of [1,3]thiazolo[3,2-b][1,2,4]triazoles were synthesized using an accessible protocol based on electrophilic heterocyclization and were characterized using infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, and their in vitro antimicrobial and antifungal activities were evaluated using the agar plate diffusion method and the microdilution plate procedure. Both antibacterial (Gram-positive and Gram-negative) and antifungal activities were found for the examined samples. The minimum inhibitory concentration (MIC) varied from 0.97 to 250 µg/mL, and the minimum bactericidal concentration (MBC) from 1.95 to 500 µg/mL. Compound 2a showed good antifungal action against Candida albicans and Saccharomyces cerevisiae with minimum fungicidal concentration (MFC) 125 and MIC 31.25 µg/mL. The molecular docking revealed that the 2-heptyl-3-phenyl-6,6-trimethyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium cation stands out as a highly promising candidate for further investigation due to a wide range of interactions, including conventional hydrogen bonds, π-σ, π-π T-shaped, and hydrophobic alkyl interactions. The synthesis and preliminary evaluation of [1,3]thiazolo[3,2-b][1,2,4]triazoles yielded promising antimicrobial and antifungal candidates. The diverse interaction profile of the 2-heptyl derivative salt allows this compound's selection for further biological studies.

Background: The outbreak of the global pandemic COVID-19 has infected and killed more than millions of people in a short period of time. Given the condition, there is an urgent need for developing anti-viral therapy for eradicating the coronavirus. Plant metabolites remain to be valuable resources in treating various ailments, including viral diseases. Since Clausena anisata (CA) has been reported for its antiviral activity, exploration of anti coronavirus activity will lead to the development of anti coronavirus drug molecules. Protease enzymes play a crucial role in the process of converting the core proteins into structural and functional proteins,which is essential for the survival of coronavirus life cycle. Hence, proteases, such as main protease and papain like protease, were selected therapeutic targets to explore the anti-COVID activity of CA. Objectives: The present study aims to carry out insilico molecular docking, ADME-Tox prediction and molecular dynamic studies to unfold the possible protease inhibitory activities of phyto principles of CA against main protease (Mpro) and papain like protease (PLpro) of SARS-CoV-1& 2. Methods: All the insilico studies were carried out using Schrödinger software. Molecular docking studies were carried out targeting main protease (PDB ID: 2GTB, 6LU7) and papain-like protease (PDB ID: 4OW0, 7CMD), which were retrieved from the Protein Data Bank (PDB). Studies were also conducted on the absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses. Molecular dynamic simulation study was carried out to observe the behaviour of the Ligandtarget complex and to calculate the stability over time on the top-scored phytoprinciples of CA. Results and Discussion: Out of 139 phyto principles selected for the study, some phytoprinciples, such as Heptaphylline, Clausenamide, indicolactone, and xanthotaxol showed better docking scores. The phytoprinciples of CA interacted with Mpro and PLpro of both SARS-CoV-1& 2. These phyto compounds were found to have molecular interaction with the essential amino acid residues, such as TYR 268, ASP 164, GLN 269, Trp106, Asn109, Lys232, Pro247, His272, Asp286 and Thr301 of PLpro and HIS 41, Glu 166 and Cys 145 of Mpro. Molecular dynamics study demonstrated the stability of the phytochemicals-target complexes. ADME-Tox prediction results showed the drug likeness and non-toxic nature of the phytoprinciples selected for the study. Conclusion: The anti-coronavirus activity of CA was explored by in silico studies. The molecular docking studies against proteases of SARS-CoV-1& 2 indicate that CA has the anti-coronavirus activity through interacting with the main protease and papain protease. The combined PLpro and Mpro inhibitory activity of CA will have additional benefit in restricting the survival coronaviruses. This study will be a base for exploring the anti-coronavirus activity of CA in multiple directions to obtain a novel anti COVID lead molecules.

Introduction: The indole scaffold, as a pharmacophore, is important because it exhibits many different biological and medicinal uses. For instance, the indole scaffold shows promise for treating bacterial and fungal infections. This research aims to create a series of new hybrid molecules that incorporate both indoles and imidazoles, and to test these new hybrids for their antimicrobial properties. Methods: A series of novel 2′-[2-(substituted phenyl)-4,5-diphenyl-1H-imidazol-1-yl phenyl]-1Hindole derivatives (4a–4j) were synthesized via the condensation of 2-(o-aminophenyl)indole with various aromatic aldehydes in ethanol using acetic acid as a catalyst. The reaction progress was monitored by Thin-Layer Chromatography (TLC), and products were purified by recrystallization. Structural elucidation was carried out using FT-IR, ¹H-NMR, ¹³C-NMR, mass spectrometry, and elemental analysis. results: All synthesized derivatives were evaluated for their antibacterial, antifungal, and anticancer activities. Compounds 4e, 4f, and 4k demonstrated significantly enhanced antimicrobial effects. Molecular docking studies further supported these findings, revealing strong binding affinities of the active compounds with key biological targets such as DNA Gyrase B and Lanosterol 14-α demethylase. Results: All synthesized compounds were screened for antibacterial and antifungal activities. Compounds 4e, 4g, and 4j demonstrated superior antimicrobial activity. Molecular docking studies revealed strong binding affinities with DNA Gyrase B and Lanosterol 14-α demethylase, correlating with the experimental findings. Discussion: The other biological activities, especially antimicrobial, were found in some selected derivatives, indicating that these indole-imidazole hybrids have good potential to act as lead compounds in the field of antimicrobial drug development. Conclusion: The synthesized indole–imidazole derivatives represent promising lead scaffolds for further development as antimicrobial agents.

The ongoing quest for multifunctional organic molecules that exhibit both pharmaceutical and optoelectronic potential has intensified interest in heterocyclic compounds. Among them, hydrazone derivatives stand out for their diverse biological activities, including antimicrobial, antiviral, and anticancer properties, as well as their tunable electronic and optical properties. The presence of the –C N–NH– linkage enables effective conjugation and charge transfer, enhancing their chemical reactivity, stability, and nonlinear optical (NLO) behaviour. Owing to these versatile features, the design and synthesis of novel hydrazone-based heterocycles have gained prominence for potential applications in drug development and advanced material science. This study focuses on the design, synthesis, and characterization of a novel hydrazone derivative, N′-((2,3-dihydrobenzo[ b ][1,4]dioxin-6-yl)methylene)furan-2-carbohydrazide (DDMF). The compound combines furan and benzo dioxane moieties to enhance conjugation and biological activity. Its structural, electronic, and reactive properties were examined using FT-IR, ¹H NMR, ¹ ³C NMR, and DFT-based quantum chemical analyses. In addition, molecular docking and ADMET studies were performed to evaluate its binding affinity, drug-likeness, and pharmacokinetic behaviour, providing insight into its potential pharmaceutical and optoelectronic applications. The DDMF compound was synthesized and structurally confirmed using FT-IR, ¹H NMR, and ¹ ³C NMR spectroscopy. Theoretical investigations were carried out using Density Functional Theory (DFT) to study molecular geometry, electronic structure, and reactivity descriptors. Frontier Molecular Orbital (FMO), Natural Bond Orbital (NBO), and Molecular Electrostatic Potential (MEP) analyses were performed to assess charge distribution and reactive sites. In addition, UV-Vis, NLO, and molecular docking studies were conducted alongside ADMET and drug-likeness evaluations. The optimized geometry showed excellent correlation with experimental data, exhibiting minimal RMSD in bond lengths (0.020 Å) and bond angles (5.20°). FMO analysis revealed moderate reactivity and effective charge transfer, while NBO and MEP confirmed significant electron delocalization. The compound exhibited strong NLO activity and consistent NMR spectral agreement (¹H RMSD = 0.437 ppm; ¹³C RMSD = 1.24 ppm). UV-Vis spectra indicated distinct π→π* transitions at 275 and 350 nm. Docking studies showed stable interactions of DDMF with SARS-CoV-2 targets, supported by stable RMSD (∼1–2.5 Å) and low RMSF values. The compound demonstrated excellent intestinal absorption (94.63 %), favorable ADMET profiles, and high drug-likeness (MW 272.26 g/mol, LogP 1.84, TPSA 73.06 Ų). The combined experimental and theoretical investigations unequivocally confirm the successful synthesis, structural integrity, and stability of the DDMF molecule. The compound exhibits favorable electronic configuration, optical responsiveness, and pharmacological potential, as evidenced by its consistent spectroscopic characteristics, strong charge-transfer behaviour, and stable molecular interactions with biological targets. The integration of computational and spectroscopic analyses establishes DDMF as a structurally robust and functionally versatile molecule, making it a promising candidate for future advancements in both optoelectronic device fabrication and therapeutic drug development. • Synthesis of novel hydrazone derivative. • Investigation of electronic properties through DFT-based analysis. • Molecular docking analysis to evaluate the inhibitory potential of the synthesized compound. • Molecular dynamics simulation conducted over a 100 ns period to examine the dynamic interactions between the protein and ligand.