Traditional medicines have reportedly treated SARS-CoV-2 infection. Substantial evidence shows that fish oil supplements promote human immune function, suggesting they may lessen susceptibility to SARS-CoV-2 infection and suppress viral replication by inducing interferon. Fish oil was subjected to partition chromatography and separated into two compounds (EP01 and DH01). Isolated compounds were purified and characterized using UV, FTIR, NMR, and mass spectrometry to confirm their identity. Molecular docking was studied on the SARS CoV-2 variants of concern; SARS CoV-2 WT (PDB: 6VXX), SARS CoV-2 Alpha variant (PDB: 7LWS), SARS CoV-2 Delta variant (PDB: 7TOU), SARS CoV-2 Gamma variant (PDB: 7V78), SARS CoV-2 Kappa variant (PDB: 7VX9), and SARS CoV-2 Omicron variant (PDB: 7QO7) and TMPRSS2 (PDB: 7Y0E). Further selected protein-ligand complexes were subjected to 100 ns MD simulations to predict their biological potential in the SARS-CoV-2 treatment. In-vitro biological studies were carried out to support in-silico findings. Isolated compounds EP01 and DH01 were identified as 5-Tridecyltetrahydro-2H-pyran-2-one and 5-Heptadecyltetrahydro-2H-pyran-2-one, respectively. The compound EP01 significantly reduced (93.24 %) the viral RNA copy number with an IC50 of ~8.661 μM. EP01 proved to be a potent antiviral by in-vitro method against the SARS-CoV-2 clinical isolate, making it a promising antiviral candidate, with a single dose capable of preventing viral replication.

Kirsten rat sarcoma (KRAS) stands out as the most prevalent mutated oncogene, playing a crucial role in the initiation and progression of various cancer types, including colorectal, lung and pancreatic cancer. The oncogenic modifications of KRAS are intricately linked to tumor development and are identified in 22% of cancer patients. This has spurred the necessity to explore inhibition mechanisms, with the aim of investigating and repurposing existing drugs for diagnosing cancers dependent on KRAS G12C In this investigation, 26 nucleoside-based drugs were collected from literature to assess their effectiveness against KRAS G12C. The study incorporates in-silico molecular simulations and molecular docking examinations of these nucleoside-derived drugs with the KRAS G12C protein using Protein Data Bank (PDB) ID: 5V71. The docking outcomes indicated that two drugs, Azacitidine and Ribavirin, exhibited substantial binding affinities of -8.7 and -8.3 kcal/mol, respectively. These drugs demonstrated stability in binding to the active site of the protein during simulation studies. Root mean square deviation (RMSD) analyses indicated that the complexes closely adhered to an equilibrium RMSD value ranging from 0.17 to 0.2 nm. Additionally, % occupancies, bond angles and the length of hydrogen bonds were calculated. These findings suggest that Azacitidine and Ribavirin may potentially serve as candidates for repurposing in individuals with KRAS-dependent cancers.Communicated by Ramaswamy H. Sarma.

Sulfonamide derivatives have numerous pharmaceutical applications having antiviral, antibacterial, antifungal, antimalarial, anticancer, and antidepressant activities. The structural flexibility of sulfonamide derivatives makes them an excellent candidate for the development of new multi-target agents, although long-time exposure to sulfonamide drugs results in many toxic impacts on human health. However, sulfonamides may be functionalized for developing less toxic and more competent drugs. In this work, sulfonamides including Sulfapyridine (a), Sulfathiazole (b), Sulfamethoxazole (c), and Sulfamerazine (d) are used to synthesize Schiff bases of 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbalde-hyde (1a-1d). The synthesized compounds were spectroscopically characterized and tested against hospital isolates of three Gram-positive (Methicillin-resistant Staphylococcus aureus PH217, Ampicillin-resistant Coagulase-negative Staphylococcus aureus, multidrug-resistant (MDR) Enterococcus faecalis PH007R) and two Gram-negative bacteria (multidrug-resistant Escherichia coli, and Salmonella enterica serovar Typhi), compared to the quality control strains from ATCC (S. aureus 29213, E. faecalis 25922, E. coli 29212) and MTCC (S. Typhi 734). Two of the four Schiff bases 1a and 1b are found to be more active than their counterpart 1c and 1d; while 1a have showed significant activity by inhibiting MRSA PH217 and MDR isolates of E. coli at the minimum inhibitory concentration (MIC) of 150 μg/mL and 128 μg/mL with MBC of 1024 µg/mL, respectively. On the other hand, the MIC of 1b was 150 μg/mL against both S. aureus ATCC 29213 and Salmonella Typhi MTCC 734, compared to the control antibiotics Ampicillin and Gentamycin. Scanning electron microscopy demonstrated the altered surface structure of bacterial cells as a possible mechanism of action, supported by the in-silico molecular docking analysis.

UNASSIGNED: The goal of the present study is to examine pretreatment with Schiff bases and derivatives of pregabalin along with their metal (Zn and Cu) complexes on the severity of epilepsy, latency time, duration of convulsions, seizure score and survival rate in mice.
UNASSIGNED: To achieve the goal, a molecular docking study of analogues was carried out on a specific molecular target, such as the alpha-2δ receptor (PDB ID: 6ND9); which revealed the significant binding affinity of the analogs to their respective target. Based on the docking information, all pregabalin derivatives were synthesized and in-vivo antiepileptic effect was confirmed by applying the PTZ model that prioritized the most crucial significant points responsible for biological activity.
UNASSIGNED: The test compounds markedly increased the latency of the first seizure and reduced the frequency of seizures throughout the body and frequent spinning and jumps. Additionally, treatment with pregabalin derivatives in mice that received PTZ significantly reduced the duration of seizures and seizure score. However, it increased the survival rate of the mice.
UNASSIGNED: Since the newly synthesized compounds were more active as compared to the parent drug in some respects; therefore, the expansion of the project can be planned to explore clinical side of the drugs in the future.
Docking studies of Schiff bases and derivatives of Pregabalin along with their Zn and Cu metal complexesPretreatment with Schiff bases and derivatives of pregabalin along with their metal (Zn and Cu)PTZ Model of epilepsyObservation of different parameters including; the severity of epilepsy, latency time, duration of convulsions, seizure score and survival rate in miceNewly synthesized compounds were more active as compared to the parent drug.

Derivative synthesis has been a crucial method for altering the effects of already-approved medications, especially to lessen adverse effects and enhance results. Making use of this multi-target approach, a series of naproxen-sulfa drug conjugates was designed and synthesized. The newly designed conjugates were confirmed by spectroscopic techniques like IR, 1HNMR, 13CNMR, and elemental analysis. The conjugates were screened for anti-inflammatory, urease, and cyclooxygenase-2 (COX-2) inhibition. Naproxen conjugated with sulfanilamide, sulfathiazole, and sulfaguanidine was found potent and showed a competitive mode of urease inhibition, with IC50 (µM) values 6.69 ± 0.11, 5.82 ± 0.28, 5.06 ± 0.29, respectively. When compared to other screened conjugates, the naproxen-sulfamethoxazole conjugation showed better anti-inflammatory action by inhibiting induced edema by 82.8%, which is comparable to the medication indomethacin (86.8% inhibition). Whereas it exhibited 75.4% inhibition of COX-2 at 10 µM concentration which is comparable with the reference drug (celecoxib, 77.1% inhibition). Moreover, the binding modes of competitive inhibitors with the urease and COX-2 receptor were predicted through molecular docking studies and their stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and there were no conformational changes that occurred during simulation. The obtained results showed that the conjugates of approved therapeutic molecules may lead to the development of novel types of pharmacological agents in the treatment of several pathological disorders where urease and COX-2 enzymes are involved.

The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is responsible for ongoing epidemics in humans and some other mammals and has been declared a public health emergency of international concern. In this project, several small non-peptide molecules were synthesized to inhibit the major proteinase (Mpro) of SARS-CoV-2 using rational strategies of drug design and medicinal chemistry. Mpro is a key enzyme of coronaviruses and plays an essential role in mediating viral replication and transcription in human lung epithelial and stem cells, making it an attractive drug target for SARS-CoV. The antiviral potential of imidazoline derivatives as inhibitors of (SARS-CoV-2) Mpro was evaluated using in-silico techniques such as molecular docking simulation, molecular dynamics (MD), and ADMET prediction. The docking scores of these imidazoline derivatives were compared to that of the N3 crystal inhibitor and showed that most of these compounds, particularly compound E07, interacted satisfactorily in the active site of the coronavirus and strongly interacted with the residues (Met 165, Gln 166, Met 165, His 41, and Gln 189). Furthermore, the results were confirmed by MD simulations after exposure to long-term MD simulations and ADMET predictions.

Herein we report a catalyst, metal and additive free generation of carbonyl ylides by blue LED irradiation of aryl diazoacetates in presence of aldehydes. The resulting ylides underwent [3+2] cycloaddition with substituted maleimides present in the reaction mixture to afford 4, 6-dioxo-hexahydro-1H-furo[3, 4-c] pyrrole in excellent yields. Fifty compounds were synthesized based on this scaffold. Molecular docking indicated them to be potential poly ADP ribose polymerase (PARP) inhibitor. Screening a representative member of the library against PARP-1 enzyme revealed a few potential inhibitors with IC50 of 600-700 nM. The phenotypic screening against MCF7, A549 and HepG2 cells furthermore indicated that these compounds selectively inhibit the proliferation of A549, HeLa and HepG2 cells with IC50 of 1-2 μM. The mechanism of action of the most active compound at the cellular level was investigated.

Sertraline Hydrochloride (STH) is an antidepressant drug that belongs to the selective serotonin reuptake inhibitor family (SSRIs), which inhibits serotonin uptake in presynaptic nerve fibers. The use of these medications without a legitimate prescription might result in adverse effects, and in rare circumstances, death. The interaction mechanism and binding mode of STH with duplex DNA were extensively investigated using spectroscopic and modeling techniques at different temperatures. The hypochromic shift of the absorption spectra of STH on binding with CT-DNA indicated groove binding. Fluorescence spectroscopic studies showed that CT-DNA quenches the fluorescence intensity of STH through a static quenching mechanism. The thermodynamic parameters indicated that the complex formation was spontaneous, and enthalpy driven. The competitive displacement binding study revealed that STH displaced DAPI from the minor groove of DNA. Molecular docking and molecular dynamics simulations also revealed that the complex was stable over 150 ns and that STH preferred the minor groove of DNA. The binding energy of the stable conformations were evaluated through MM/PBSA methods. A comparison of the bound poses at different timescales showed minor changes in STH structure upon DNA binding. Furthermore, a structural analysis of CT-DNA indicated that STH induced changes in the sugar-phosphate backbone had an impact on the minor groove\'s width which are in agreement with the CD spectroscopic results. This study provides a better understanding of STH binding with duplex DNA.

BACKGROUND: Mucormycosis has been infesting the universe for a while back, often with no prompt treatments. The disease devastation is spreading at an alarming rate. Many researchers are still hoping for a good potential drug that could help the healthcare system in this tussle. Molecular docking is an in silico tool that has gained popularity over the last few decades. Knowing the mechanism of enzymatic action is aided by imitating membrane protein actions in binding ligands.
OBJECTIVE: The aim of this perspective is to determine whether an existing drug, daclatasvir, has antifungal activity.
OBJECTIVE: The primary objective of this in silico study was to investigate the potential effects of the binding affinity of daclatasvir with the crucial protein (1XFF) of mucormycosis, as well as the binding pattern of the active site amino acids with the drug molecule.
METHODS: To calculate the binding affinity of daclatasvir to the fungal protein 1XFF, Auto Dock Vina was used for molecular docking studies. The CDOCKER protocol was used to determine the receptor-ligand interaction by configuring various parameters.
RESULTS: The docking energy of the ligand (daclatasvir) on the protein (1XFF) was found to be -16.7216 kcal/mol, while the interaction energy was found to be - 42.1314 kcal/mol.
CONCLUSIONS: The binding pattern completely alters the dynamics of the protein, resulting in the breakdown of the fungal wall. The vital protein (1XFF) of Rhizopus oryzae is proposed as a possible protein target for the non-structural protein 5A inhibitor/antiviral drug daclatasvir in this study.

Duranta erecta Linn. has a longstanding history for use in folk remedy for several disorders. Its hydroalcoholic extract has been investigated intensely in the treatment of many ailments, but to date very few data are presented to explain the pharmacological use of its oil. In this study, the chemical profiles of the leaf oils extracted from three Egyptian Duranta erecta cultivars, namely \'Green\', \'Golden edge\', and \'Variegata\' are traced using GC-MS analysis. D. erecta \'Green\' showed predominance of vitamin E (22.7%) and thunbergol (15%) whereas D. erecta \'Golden edge\' and \'Variegata\' contained tetratetracontane as a major component in their oils. The highest phenolic and flavonoid contents, displayed as gallic acid and rutin equivalents per gram oil, respectively, were observed in the \'Golden edge\' and \'Variegata\' cultivars, which was reflected by their strong DPPH and ABTS scavenging activities as well as the highest reducing power in both CUPRAC and FRAP assays. D. erecta \'Green\' displayed better metal chelating potential, which may be attributed to its content of vitamin E. All cultivars showed similar enzyme inhibitory profiles. The best inhibition of α-glucosidase and α-amylase was observed by D. erecta \'Green\'. In silico studies of the major constituents docked on the active sites of the target enzymes NADPH oxidase, amylase, glucosidase, butyrylcholinesterase, and tyrosinase revealed high binding scores, which justified the biological activities of the tested oils.