The outbreak of SARS-CoV-2 creates the biggest crisis to human health and adversely affects the economic growth worldwide. Recently, several vaccines have been emerged by the manufacturers to combat COVID-19. Unfortunately, no therapeutic medication has yet been approved by FDA for the treatment of this disease. In this aspect, several research groups have paid attention to find out the potential SARS-CoV-2 protein inhibitors from the bio-molecules available in medicinal plants, spices, and vegetables. In this paper, we have performed the structure-based virtual screening (VS) of 120 compounds derived from Nigella sativa (NS) against M^pro, PL^pro and Spike proteins of SARS-CoV-2. Strong binding interactions of M^pro occurred with hits NS-40, and NS-84 whereas hits NS-72D and NS-95D showed strong binding interaction with Spike protein. Interestingly, four promising hits namely NS-21, NS-40, carvacrol and menthol exhibited good binding interactions with both M^pro and Spike proteins. It was observed that carvacrol, a monoterpenoid phenol exhibited several biological activities, has favourable binding affinity towards papain-like protease of SARS-CoV-2. This small molecule may be used as a natural weapon to combat the COVID-19.

Recently, a series of fifty 4-{[(benzyloxy)carbonyl]amino}-2-hydroxybenzoic acid amides designed as potential acetyl- and butyrylcholinesterase (AChE/BChE) inhibitors have been described as potential drugs to alleviate the symptoms of Alzheimer's disease (AD). Some of these compounds have shown promise for inhibiting either AChE or BChE. Since these compounds are structurally similar to agents inhibiting beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), the aim of the contribution was to verify how our compounds are able to affect this enzyme, which, when inhibited, blocks the formation of beta-amyloid, but whose inhibition is associated with significant negative effects in humans. At a concentration of 10 µM, only benzyl {4-[(4-fluorophenyl)carbamoyl]-3-hydroxyphenyl}carbamate was found to show approximately 30% inhibition of BACE activity.

In this survey, novel Pd catalysts supported on Chitosan and EDTA were prepared for the first time and their structures were appropriately demonstrated by various analytical and identification techniques including FT-IR, EDX, XRD, SEM, TEM, TGA, DRS and BET. The Catalysts were successfully employed in the Heck Cross-Coupling Reactions (HCR) with good to excellent yields. Different aryl halides carrying Br, Iodine and Cl were used in the HCR with different acrylates to synthesis cinnamic acid and its valuable ester derivatives. The catalysts show a variety of advantages such as excellent thermal stability, easy recovery by simple filtration, more than five cycles of reusability with no significant decrease in their efficacy, biodegradability, biocompatibility and brilliant result in the HCR with low loaded Pd on the substrate.

Polypeptides have been obtained for use as carriers in polymer dosage forms containing macro- and microelements. It has been established that the optimal conditions for obtaining water-soluble polypeptides with an average molecular weight of 70,000-75,000 kDa with a maximum yield by hydrolysis of the silkworm cocoon (Bombyx mori) with caustic alkali solutions (NaOH, KOH) are: the concentration of the alkali solution is 0.250 N, the temperature of the system is 373 K, the reaction time is 80 minutes. Research has determined that the resulting polypeptides do not have a negative impact on the health of animals, do not cause local irritant effects on the skin and mucous membranes of the eyes, and do not have a cumulative property.

In this paper we reported the synthesis of new hydroxamic acids, containing heteroaromatic fragment of acridine-9(10H)-one. These compounds were prepared by interaction of corresponding carboxylic acid with hydroxylamine hydrochloride in the presence of CDI in DMF solution. The structure of obtained compounds was confirmed by IR, Mass-spectrometry, 1 H and 13 C NMR analyzed methods. Obtained compounds were screened for their in vitro antimicrobial activity against five bacterial and one fungal pathogens. Some synthesized compounds showed high efficiency against gram-positive strain Bacillus subtilis and gram-negative strain Proteus vulgaris.

Schiff bases have been important compounds ever since their discovery and are both found in nature and synthesized in the laboratory. They participate in a variety of synthetic processes and possess desirable biological activity, including antibacterial, anti-inflammatory, antioxidant, and anticancer activity, among others. In this study, eight Schiff bases derived from the reaction of 4-aminoantipyrine with various cinnamaldehydes have been synthesized and characterized. All derivatives were tested in vitro on several human carcinoma cell lines to determine their antitumor activity and against different bacteria strains of clinical and food industry importance to evaluate their antibacterial activity. Various of the Schiff bases evaluated inhibited tumor cell growth in a dose-dependent manner. The compound that exhibited the most activity against all cell lines had IC₅₀ values of less than 18 μM, and the compound with the best therapeutic index presented IC₅₀ values between 24 – 48 μM. On the other hand, during the evaluation of the antibacterial activity, only two Schiff base derivatives showed interesting antibacterial effects, with MIC values ranging from 250 – 15.6 μM. These two Schiff bases derivatives mainly exhibited a bacteriostatic effect against most of the studied bacterial strains. It is interesting to note that the same Schiff base presents the best activity in both biological evaluations.

Zinc-containing enzymes play essential roles in bacteria. From the other hand, fluorescent properties of a compound provide a way for it selective and sensitive detection. Here we report about fluorescent derivative with zinc-binding groups, namely, 7-nitrobenzofurazan-4-yl (NBD) 2-picolylamine (NPic2, AKOS008922865), ciprofloxacin 2-picolyl carboxamide (CPFPic2, a homologue of AKOS005560555) and N-NBD-ortho-phenylenediamine (NDBOPD, SCHEMBL19269457). Using the docking-based virtual screening approach and Autodock Vina, MGL Tools and helper program FYTdock we have found that NDBOPD can be bound close to Zn2+ of bacterial metallolactamases (PDB id 2P50) showing docking score from -8.9 to -9.0. Analogously, NPic2 was shown to be able to be bound close to Zn2+ of N-acetyl-D-Glucosamine-6-Phosphate deacetylase of Escherichia coli (2P50), Mycobacterium tuberculosis fructose 1,6-bisphosphate aldolase (3ELF), Staphylococcus aureus 3-dehydroquinate synthase (1XAH) and 10 more enzymes with docking score from -7.0 to -8.9, whereas CPFPic2 demonstrated such binding for Bacillus subtilis M32 carboxypeptidase (3HQ2), E. coli Oligoribonuclease (2IGI) and 10 more. Also, the energies of the ground S0 and excited S1 states, the energy levels of the HOMO and LUMO and chemical reactivity descriptors were calculated for NBD-derivatives using the density functional theory at B3LYP/6-31+ g(d,p) level. The compounds were synthesized using SnAr NBD-ylation with NBD-Cl and conjugation using N-hydroxysuccinimide/carbodiimide. Solvatochromic effects together with albumin binding tryptophan fluorescence quenching data were received. Our results support further in vitro antibacterial test opening a way to new “weapon” against pathogenic bacteria.
The work was supported by grants GPSR № 20210560, BRFFI X21-131 as well as Wargaming Stipend grant for V.Z.

As a result of the development of 4^th and 5^th generation recyclable batteries, new materials are one of the critical topics in current studies, especially for electrolyte and electrode designs. In the latest years, research related to new electrochemical materials has experienced a great upgrade. One of the most promising materials are ionic liquids (ILs), which are organic salts formed by a cation and an anion whose melting point is below 100ºC. The tuneability of the properties of ILs from the infinity combinable anions and cations and the possibility of introducing functional groups in their alkyl chains, make these fluids appropriate for many industrial applications as for example, electrolytes in mixtures of ILs and inorganic salts, mainly lithium salts.

ILs confinement in a matrix scaffold improves safety manipulation while reducing the possibility of spillage. This immobilization of ionic liquids (or mixtures with inorganic salts) is known as gelation, and the resulting material is denominated ionogel or ionic gels.

The purpose of this work is to compare the physicochemical character of two different gelation methods. One of them polymeric using Poly (vinylidene fluoride) (PVDF) as supporting matrix, and the other one sol-gel by using a silica matrix. The selected IL is N-butyl-N-methyl-pyrrolidinium bis(trifluoromethanesulfonyl)imide [BMPyrr][TFSI] and its binary mixture with [Li][TFSI] salt at different concentrations.

Recently, multi-component, one-pot reactions have been shown to be efficient and environmentally friendly methods compared to traditional linear-step syntheses. It is novel, complex and functionally dense heterocyclic molecules. Pyrazole moieties are ubiquitous in organic compounds and have a wide range of pharmacological activities, such as antitumor, antifungal, and analgesic activities. Therefore, compounds containing pyrazole rings are widely used in the fields of medicine and life sciences. In addition, pyrazoles have also shown applications in the preparation of organometallic complexes, supramolecular and electroluminescent materials, and as essential ligands for metals. Due to their excellent properties, extensive efforts have been made to construct pyrazole derivatives. Over the past few decades, various methods of constructing pyrazoles have been developed. But the most common strategy is condensation reaction between hydrazine and a 1,3-electrophilic substrate to obtain pyrazole derivatives. Therefore, the synthesis of pyrazole derivatives is an important issue. In the present work, we have described a new, efficient and environment benign synthetic method for the formation of pyrazoles through one-pot method using heterogeneous catalysis.

The WHO database shows that Mycobacterium tuberculosis has become an epidemic worldwide due to its pathogenicity and virulence, which have magnified its infectiousness. The situation becomes grimmer with the prevalence of MDR-TB, XDR-TB, emergence of cross-resistance, ineffectiveness of novel therapeutic targets, failure of novel medications in clinical trials, currently available drugs losing their therapeutic efficacy, lack of drug discovery efforts due to poor ROI, and the existence of co-infections, i.e., HIV, TB, COVID, and HIV-TB-COVID. This emphasizes the necessity of employing novel chemical entities functioning through unique mechanisms to combat the growing threat of this infectious killer disease worldwide. In this perspective, we are applying the concept of Prof. Luis E. N. Quadri, who speculated that discovering new antibacterial drugs could be facilitated by focusing on a conditionally necessary pathway in the host-pathogen machinery. One such machinery is the mycobactin biosynthesis pathway (MBP), which helps in the mycobacterial life cycle and replication. Mycobactin (siderophore) is synthesized by the mycobactin megasynthase cluster, which includes 14 conditionally essential genes (mbtA-mbtN) and encodes a mixed nonribosomal peptide synthetase-polyketide synthase (NRPS-PKS) system. Of which the enzyme salicyl-AMP ligase (MbtA) plays a pivotal role. This makes it a promising endogenous target for identifying new lead molecules/inhibitors. Since the 2000s, nucleoside analogs have been the focus of much research as potential MbtA inhibitors. Since these have poor PK profiles, our research group is more diverted toward identifying non-nucleoside analogs. Following our prior studies described by Stirret et al., 2008, Ferreras et al., 2011, & Shyam et al., 2021 herein we focus on exploring pyrazoline-based mycobactin analogs (non-specific mycobactin biosynthesis inhibitors) targeting MbtA enzyme (1^st step of mycobactin biosynthesis) with a hope of finding a more potent analog showing a high affinity for MbtA. Design strategy involves retaining the structural features of mycobacterial siderophores. Hence, we designed a small library (12 molecules) of mycobactin analogs keeping the necessary scaffold (diaryl-substituted pyrazoline (DAP)) intact and assessed their insilico stability using molecular docking simulations (AutoDock 4.2.6) and molecular dynamics simulations (GROMACS) to identify second-generation hit-compounds. To find the binding modalities and inhibitory profile of the proposed compounds, they were docked in the active site of the MbtA receptor (by analogy with the homologous structure PDB: 1MDB). The lowest energy conformation of each docked ligand (best score) was visualized. The six top-scoring compounds were evaluated for their ADMET (absorption-distribution-metabolism-excretion-toxicity) profile. The best molecule which revealed a good ADMET profile were taken up for MD simulation study (45ns). Results revealed that the designed compound GV02 (-8.53, 563.3nM), GV03 (-8.59, 508.51nM), GV04 (-8.26, 878.26nM), GV07, (-8.54, 553.44nM), GV08 (-8.80, 352.58nM), and GV09 (-8.61, 499.91nM) had good docking score and inhibition constant. Of these GV08 showed a good ADME profile with all major parameters lying in the acceptable ranges. They also showed the least toxicity with no hepatotoxicity and skin sensitization. MD simulation studies of GV08 also suggest that the protein-ligand complex is stable throughout the simulation as was evidenced by RMSD, RMSF, and H-bond plots. The future scope invalidates these findings through synthesis, characterization, and intracellular activity.