Journal of Computational Biophysics and Chemistry

Bladder and prostate cancers are among the most prevalent malignancies in men, posing challenges in treatment and prognosis. This study aimed to evaluate the expression of the oncogenes TOP2A, UBE2C and CKS2 in the bladder (BLCA) and prostate (PRAD) cancers and assess the potential inhibitory effects of sitagliptin through molecular docking. Microarray datasets from the NCBI–GEO database were analyzed to identify differentially expressed genes (DEGs), visualized using volcano plots, UMAP and Venn diagrams. TOP2A, UBE2C and CKS2 expression levels were linked to cancer progression, with mutation and interaction analysis performed using cBioPortal, STRING and GeneMANIA. In silico docking evaluated the binding affinity of sitagliptin, PNU-74654 and Crizotinib. Results showed significant overexpression of TOP2A, UBE2C and CKS2 in advanced stages of BLCA and PRAD, correlating with poorer survival. Sitagliptin exhibited strong binding affinities (−178.98, −125, −112 kcal/mol) to these oncogenes, suggesting its inhibitory potential. PNU-74654 and Crizotinib showed lower binding affinities. This study highlights sitagliptin as a promising therapeutic agent targeting TOP2A, UBE2C and CKS2, with potential to reduce cancer cell proliferation and induce apoptosis. These findings support the development of personalized treatment approaches for bladder and prostate cancer.

SARS-CoV-2, the new coronavirus variant, has been a worldwide health crisis that may outbreak at any time in the future. Over spans of human history, preparations derived from natural products have always been recognized as a preliminary source of medications. Taking into account the SARS-CoV-2 main protease (Mpro) as the essential element of the viral cycle and as a main target, herein we highlight a computer-aided comprehensive virtual screening for a focused chemical list of 14 laulimalides marine macrolides against SARS-CoV-2 Mpro using a set of integrated modern computational techniques including molecular docking (MDock), molecule dynamic simulations (MDS) and structure–activity relationships (SARs). Based on their remarkable ligand-protein energy scores and relevant binding affinities with SARS-CoV-2 (Mpro) pocket residues, two promising macrolides [laulimalides LA4 (6) and LA18 (13)] are selected as proposed inhibitor compounds. Consequently, they are thermodynamically investigated by deciphering their MD simulations at 100 ns, where they show noticeable stability within the accommodated (Mpro) pockets. Moreover, in-depth SARs studies suggest crucial roles for C-23 substituted side chain and C-20 methoxy as essential pharmacophoric structural features for activity. Further in vitro/vivo examinations of the selected marine macrolides would pave the way towards developing effective antiviral drugs from natural resources.

This work characterizes microemulsions of Medicago marina essential oil and evaluates their antimicrobial, antibiofilm, and anticoagulant effects. Medicago marina L. aerial parts essential oil was hydro-distilled and analyzed by gas chromatography-FID and gas chromatography/mass spectrometry (GC/MS) for the first time from the Tunisian chemotype. The microemulsion was prepared using an oil/water formulation with a biopolymer (Arabic gum) and surfactant (Tween 20). Antibacterial and antifungal activities were evaluated using the microbroth dilution method, while anticoagulant activity was tested in vitro using prothrombin time (PT) and aPTT tests. Eventually, the binding affinities and molecule’s interactions of the main chemicals with the operational locations of C (30) carotenoid dehydrosqualene synthase and cytidine deaminase were explored. The essential oil contained 71 compounds of which 87.6% were identified. Major compounds were $\beta$-ionone (17.67%), 1-methyleugenol (10.75%), eugenol (8.86%), $\beta$-damascenone (4.33%), and $\alpha$-humulene (4.32%). A microemulsion with a diameter of 1.63 $\mu$m, a polydispersity index of 0.17, a zeta potential of –40.8 mV and a pH of 6 was obtained and it showed the highest antibacterial potential against a multitude of microbes, with low MICs varying between 0.406 mg/mL and 3.25 mg/mL. Significant antibiofilm activity was observed with over 80% inhibition at 4 × MIC concentration. It showed better anticoagulant activity than heparin, with PT and aPTT values of 19.5 s and 57 s, respectively, at 10 mg/mL. Molecular docking showed that “($E)$-$\beta$-ionone” had the highest binding scores. Notable pharmacokinetic and drug-like qualities were found in the obtained molecules after establishing ADME profiling. As a result, Medicago marina L. Essential oil microemulsion can be used in food processing as a preservative.

The synthesis and characterization of a series of 5-nitro-$N$-phenyl-3-(phenylamino)-1$H$-indazole-1-carboxamide 5-NPIC derivatives (5a–5v) have been reported as anticancer agents in this study. These derivatives were synthesized by reacting 3-chloro-5-nitro-$N$-phenyl-1$H$-indazole-1-carboxamide (4) with a variety of aniline derivatives in isopropanol. FT-IR, ¹H-NMR, 13C-NMR and mass spectral methods were employed to confirm the structures of analogues (5a–5v). The anticancer activity evaluation of compounds 5a–5v revealed that 3-((3-methoxyphenyl) amino)-5-nitro-$N$-phenyl-1$H$-indazole-1-carboxamide (5j) exhibited good efficacy. The stability of ligand–protein complexes was systematically evaluated using molecular dynamics simulations (MDS), which demonstrated a consistent and robust binding of the most potent compound within the binding sites of target proteins. The results confirmed the anticancer activity, which was further substantiated by comprehensive molecular docking analyses that revealed complex interactions involving hydrophobic contacts, electrostatic forces and hydrogen bonds. Our results would collectively provide invaluable insights into the intricate molecular structure and dynamics of receptor target sites, thereby establishing a solid foundation for the development of novel and potent anticancer agents with optimistic pharmaceutical implications in near future.

Chamomile, emphasized as an herbal remedy with healing potential for human health, is used in traditional medicine. In this study, the potential of compounds derived from Matricaria chamomilla L. against IL-6, JAK-1 and TNF-$\alpha$ target proteins associated with rheumatoid arthritis (RA) was compared with known inhibitors. The drug-likeness and ADME/T properties of these compounds were investigated using online tools, and molecular docking and molecular dynamics simulations of the selected structures were examined. IL-6, JAK-1 and TNF-$\alpha$ formed stable complexes with apigenin, quercetin and galaxolide, respectively, demonstrating that these compounds exhibit potential inhibitory activity against RA.

Mycobacterium tuberculosis (Mtb), the bacterium responsible for tuberculosis (TB), employs mycolic acids to build its cell wall. This robust structure plays a vital role in protecting the bacterium from external threats and contributes to its resistance against antibiotics. Mycobacterial membrane protein Large 3 (MmpL3), a secondary resistance nodulation division transporter, is essential in mycolic acid biosynthesis, transporting mycolic acid precursors into the periplasm using the proton motive force. Due to its role in bacterial cell wall formation, it is a promising target for new tuberculosis treatments. In this study, starting with 85 known MmPL3 compounds, the artificial intelligence (AI)-assisted tool “Design of Druglike Analogues (DeLA-Drug)” was employed to generate about 15,000 novel molecules. These compounds were then subjected to structure-based high-throughput virtual screening and molecular dynamics (MD) simulations to identify potential novel inhibitors of MmpL3. The binding affinity was obtained by docking the above molecules at the SQ109 binding site in MmPL3, followed by pharmacokinetics and toxicity, which were used to reduce the chemical space. Finally, five ligands were subjected to 100 ns MD simulations to investigate the binding energetics of inhibitors to MmpL3. These compounds demonstrated stable binding and favorable drug-like properties, indicating that they could serve as potential novel inhibitors of MmpL3 for Mtb.

Although cancer has been the main reason for death for decades, until now, no safe certified drugs have been discovered to efficiently inhibit its progression. Currently, we aim to employ an in-silico model to predict the action mechanism of phenolic components that we previously demonstrated as inhibitors of colon, prostate and lung cancer. The work was performed by testing pharmacokinetics and pharmacodynamics proprieties of selected molecules. Four compounds: Kaempferol, chrysin, vanillin and p-hydroxybenzoic acid widely obeyed the five rules and the ADME/T criteria with minimum toxicity. Docking prediction recorded an intense affinity between kaempferol- CDK1(−17.72 ± 0.02 kcal/mol), chrysin-CDK1 (−17.61 ± 0.01 kcal/mol) and kaempferol-caspase 8 (−9.30 ± 0.00 kcal/mol), chrysin-caspase 8 (−8.18 ± 0.12 kcal/mol), vanillin-MMP9 (−9.83 ± 0.04 kcal/mol) and p-hydroxybenzoic acid-Ca2 (−8.91 ± 0.01 kcal/mol). Likewise, MMGBSA results demonstrated that these compounds are evidently bound to the targets’ active sites with solid interactions. The passed compounds might target the responsible factors for transcription as inactivators. The molecular mechanism based on kaempferol and vanillin actions was predicted to target CDK1 and MMP9 via cell cycle arrest and apoptosis. All results were confirmed through RMSD analysis suggesting that kaempferol and vanillin are the best ligands to suppress cancer cell proliferation. Thus, these findings allowed us to imagine a potential molecular mechanism of these binaries, phenolic compounds/target proteins to lead further trails on cancer, of which the synergistic activity between phenolic compounds could promote the therapeutic capacity.

This study investigates the photoresponsive behavior of substituted azobenzenes with a specific focus on their nonlinear optical response. This study suggests that azoimidazole substitution is a better alternative to azobenzene derivatives for nonlinear optical responses. The synthesis, characterization, photophysical property and isomerization pathway of 2-[($E)$-(4-fluorophenyl)diazenyl]-1$H$-imidazole ($E$-2g) are presented as an optical limiter through a comprehensive blend of experimental and theoretical approaches. Notably, $E$-2g exhibited a lower energy barrier than reported azobenzenes. The trans-to-cis photostationary state was reached in 75 min, while the cis-to-trans state was achieved in 60 min at 354 nm. The study further explores the photoisomerization pathway of E-2g, highlighting its nonlinear absorption, which has a nonlinear absorption coefficient ($\beta$_eff) of 8.8 × 10${}^{-11}$ m/W at 20 $\mu$J, as determined by $Z$-scan measurements. The results suggest that $E$-2g exhibits significant nonlinear absorption characteristics, which helps in applications requiring protection from intense light sources.