Advances in the Synthesis of Biologically Active Quaternary Ammonium Compounds.

This review provides a comprehensive overview of recent advancements in the design and synthesis of biologically active quaternary ammonium compounds (QACs). The covered scope extends beyond commonly reviewed antimicrobial derivatives to include synthetic agents with antifungal, anticancer, and antiviral properties. Additionally, this review highlights examples of quaternary ammonium compounds exhibiting activity against protozoa and herbicidal effects, as well as analgesic and anesthetic derivatives. The article also embraces the quaternary-ammonium-containing cholinesterase inhibitors and muscle relaxants. QACs, marked by their inherent permanent charge, also find widespread usage across diverse domains such as fabric softeners, hair conditioners, detergents, and disinfectants. The effectiveness of QACs hinges greatly on finding the right equilibrium between hydrophilicity and lipophilicity. The ideal length of the alkyl chain varies according to the unique structure of each QAC and its biological settings. It is expected that this review will provide comprehensive data for medicinal and industrial chemists to design and develop novel QAC-based products.

Enantioselective synthesis, characterization, molecular docking simulation and ADMET profiling of α-alkylated carbonyl compounds as antimicrobial agents.

All living organisms produce only one enantiomer, so we found that all natural compounds are presented in enantiomerically pure form. Asymmetric synthesis is highly spread in medicinal chemistry because enantiomerically pure drugs are highly applicable. This study initially demonstrated the feasibility of a good idea for the asymmetric synthesis of α-alkylated carbonyl compounds with high enantiomeric purity ranging from 91 to 94% using different quinazolinone derivatives. The structure of all compounds was confirmed via elemental analysis and different spectroscopic data and the enantioselectivity was determined via HPLC using silica gel column. The synthesized compounds' mode of action was investigated using molecular docking against the outer membrane protein A (OMPA) and exo-1,3-beta-glucanase, with interpreting their pharmacokinetics aspects. The results of the antimicrobial effectiveness of these compounds revealed that compound 6a has a broad biocidal activity and this in-vitro study was in line with the in-silico results. Overall, the formulated compound 6a can be employed as antimicrobial agent without any toxicity with high bioavailability in medical applications.

Targeted potent antimicrobial and antitumor oxygen-heterocyclic-based pyran analogues: synthesis and computational studies.

The process of creating a series of 3-amino-1-aryl-8-methoxy-1H-benzo[f]chromene-2-carbonitriles (4a-q) involved reacting 6-methoxynaphthalen-2-ol (1), the appropriate aromatic aldehydes (2a-q), and malononitrile (3) in an absolute ethanol/piperidine solution under Ultrasonic irradiation. However, the attempt to create 3-amino-1-aryl-1H-benzo[f]chromene-2,8-dicarbonitrile (6a, d, e) was unsuccessful when 6-cyanonaphthalen-2-ol (5) was stirred at room temperature, reflux, Microwave irradiation, or Ultrasonic irradiation. In addition, the target molecules were screened against Staphylococcus aureus (MRSA), Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Escherichia coli and Klebsiella pneumonia, as well as a panel of three human cancer cells lines such as MCF-7, HCT-116, HepG-2 and two normal cell lines HFL-1 and WI-38. The obtained results confirmed that the pyran derivatives (4 m, i, k) which have a double chlorine at 3,4/2,3/2,5-positions, a single halogen atom 3-Cl/4-Br (4c, e) and a double bromine at 3,5-positions with a single methoxy group at 2-position (4n), of phenyl ring, and, to a lesser extent, other pyran derivatives with monoihalogenated (4a, b, d, f), dihalogenated (4 g, h, j, l) or trisubstituent phenyl ring (4o, p, q). Furthermore, compounds 4b-e, g, i, j, m, and n showed negligible activity against the two normal cell lines, HFL-1 and WI-38. Moreover, compound 4 g exhibited the strongest antimicrobial activity among the other pyran derivatives (4a-f, g-q) when compared to Ciprofloxacin. The MIC was assessed and screened for compound 4 g, revealing bactericidal effects. Lastly, SAR and molecular docking were studied.

Fluorine in the pharmaceutical industry: Synthetic approaches and application of clinically approved fluorine-enriched anti-infectious medications.

The strategic integration of fluorine atoms into anti-infectious agents has become a cornerstone in the field of medicinal chemistry, owing to the unique influence of fluorine on the chemical and biological properties of pharmaceuticals. This review examines the synthetic methodologies that enable the incorporation of fluorine into anti-infectious drugs, and the resultant clinical applications of these fluorine-enriched compounds. With a focus on clinically approved medications, the discussion extends to the molecular mechanisms. It further outlines the specific effects of fluorination, which contribute to the heightened efficacy of anti-infective therapies. By presenting a comprehensive analysis of current drugs and their developmental pathways, this review underscores the continuing evolution and significance of fluorine in advancing anti-infectious treatment options. The insights offered extend valuable guidance for future drug design and the development of next-generation anti-infectious agents.

Synthesis of new quaternized chitosan Schiff bases and their N-alkyl derivatives as antimicrobial and anti-biofilm retardants in membrane technology.

New quaternized salicylidene chitosan Schiff bases (QSCSBs) and their N-octyl derivatives (OQCs) have been synthesized and characterized, aiming to develop innovative antimicrobial and anti-biofilm agents. This research holds immense potential, as these compounds could be utilized as anti-biofouling additives in membrane technology in the future. The synthesis involved the modification of low molecular-weight-chitosan (LMC) through simultaneous Schiff base formation and quaternization processes to create QSCSBs. Subsequently, QSCSBs were catalytically reduced to form quaternized N-benzyl chitosan (QBCs) intermediates, which then underwent nucleophilic substitution reactions affording N-octyl quaternized chitosans (OQCs). Characterization techniques such as elemental, spectral, and microscopic analyses were used to confirm the successful synthesis of these materials. As membrane technology relies on surface charge, QSCSBs and OQCs with large zeta potentials could be used as positively charged additives. Moreover, SEM image revealed the regular distribution of pores and voids across the additives' surfaces raises intriguing questions about their implications for membrane performance. Meanwhile, the superior antibacterial and antibiofilm potential of these materials, particularly QSCSB2 and OQC2, indicate that the utilization of these compounds as anti-biofouling additives in membrane technology could significantly improve the performance and longevity of membranes used in various applications such as water treatment and desalination.

Synthesis and characterization of antimicrobial colloidal polyanilines.

The potential application of colloidal polyaniline (PANI) as an antimicrobial is limited by challenges related to solubility in common organic solvents, scalability, and antimicrobial potency. To address these limitations, we introduced a functionalized PANI (fPANI) with carboxyl groups through the polymerisation of aniline and 3-aminobenzoic acid in a 1:1 molar ratio. fPANI is more soluble than PANI which was determined using a qualitative study. We further enhanced the solubility and antimicrobial activity of fPANI by incorporating Ag nanoparticles onto the synthesized fPANI colloid via direct addition of 10 mM AgNO3. The improved solubility can be attributed to an approximately 3-fold reduction in size of particles. Mean particle sizes are measured at 1322 nm for fPANI colloid and 473 nm for fPANI-Ag colloid, showing a high dispersion and deagglomeration effect from Ag nanoparticles. Antimicrobial tests demonstrated that fPANI-Ag colloids exhibited superior potency against Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and Bacteriophage PhiX 174 when compared to fPANI alone. The minimum bactericidal concentration (MBC) and minimum virucidal concentration (MVC) values were halved for fPANI-Ag compared to fPANI colloid and attributed to the combination of Ag nanoparticles with the fPANI polymer. The antimicrobial fPANI-Ag colloid presented in this study shows promising results, and further exploration into scale-up can be pursued for potential biomedical applications.

Synthesis, antimicrobial activity, antioxidant activity and molecular docking of novel chitosan derivatives containing glycine Schiff bases as potential succinate dehydrogenase inhibitors.

Succinate dehydrogenase (SDH) is an important inner mitochondrial membrane-bound enzyme involved in redox reactions during the tricarboxylic acid cycle. Therefore, a series of novel chitosan derivatives were designed and synthesized as potential microbicides targeting SDH and precisely characterized by FTIR, 1H NMR and SEM. Their antifungal and antibacterial activities were evaluated against Botrytis cinerea, Fusarium graminearum, Staphylococcus aureus and Escherichia coli. The bioassays revealed that these chitosan derivatives exerted significant antifungal effects, with four of the compounds achieving 100 % inhibition of Fusarium graminearum merely at a concentration of 0.5 mg/mL. Additionally, CSGDCH showed 79.34 % inhibition of Botrytis cinerea at a concentration of 0.1 mg/mL. In vitro antibacterial tests revealed that CSGDCH and CSGDBH have excellent Staphylococcus aureus and Escherichia coli inhibition with MICs of 0.0156 mg/mL and 0.03125 mg/mL, respectively. Molecular docking studies have been carried out to explore the binding energy and binding mode of chitosan and chitosan derivatives with SDH. The analyses indicated that chitosan derivatives targeted the active site of the SDH protein more precisely, disrupting its normal function and ultimately repressing the growth of microbial cells. Furthermore, the chitosan derivatives were also evaluated biologically for antioxidation, and all of these compounds had a greater degree of reducing power, superoxide radical, hydroxyl radical and DPPH-radical scavenging activity than chitosan. This research has the potential for the development of agricultural antimicrobial agents.

Impact of metal coordination and pH on the antimicrobial activity of histatin 5 and the products of its hydrolysis.

This work focuses on the relationship between the coordination chemistry and antimicrobial activity of Zn(II) and Cu(II) complexes of histatin 5 and the products of its hydrolysis: its N-terminal fragment (histatin 5-8) and C-terminal fragment (histatin 8). Cu(II) coordinates in an albumin-like binding mode and Zn(II) binds to up to 3 His imidazoles. The antimicrobial activity of histatins and their metal complexes (i) strongly depends on pH - they are more active at pH 5.4 than at 7.4; (ii) the complexes and ligands alone are more effective in eradicating Gram-positive bacteria than the Gram-negative ones, and (iii) Zn(II) coordination is able to change the structure of the N-terminal region of histatin 5 (histatin 5-8) and moderately increase all of the studied histatins' antimicrobial potency.

Total Synthesis of Dynobactin A.

The first total synthesis of the potent antimicrobial agent dynobactin A is disclosed. This synthesis enlists a singular aziridine ring opening strategy to access the two disparate ß-aryl-branched amino acids present within this complex decapeptide. Featuring a number of unique maneuvers to navigate inherently sensitive and epimerizable functional groups, this convergent approach proceeds in only 16 steps (LLS) from commercial materials and should facilitate the synthesis of numerous analogues for medicinal chemistry studies.

Revolutionizing Infection Control: Harnessing MXene-Based Nanostructures for Versatile Antimicrobial Strategies and Healthcare Advancements.

The escalating global health challenge posed by infections prompts the exploration of innovative solutions utilizing MXene-based nanostructures. Societally, the need for effective antimicrobial strategies is crucial for public health, while scientifically, MXenes present promising properties for therapeutic applications, necessitating scalable production and comprehensive characterization techniques. Here we review the versatile physicochemical properties of MXene materials for combatting microbial threats and their various synthesis methods, including etching and top-down or bottom-up techniques. Crucial characterization techniques such as XRD, Raman spectroscopy, SEM/TEM, FTIR, XPS, and BET analysis provide insightful structural and functional attributes. The review highlights MXenes' diverse antimicrobial mechanisms, spanning membrane disruption and oxidative stress induction, demonstrating efficacy against bacterial, viral, and fungal infections. Despite translational hurdles, MXene-based nanostructures offer broad-spectrum antimicrobial potential, with applications in drug delivery and diagnostics, presenting a promising path for advancing infection control in global healthcare.

New penta-Coordinated Cadmium(II) Complexes: Synthesis, Characterization, Thermal, Antimicrobial, Antioxidant and Cytotoxicity Properties.

In this paper, a new tridentate Schiff base ligand (L) with nitrogen donor atoms and its cadmium(II) complexes with the general formula of CdLX2 (X=Cl-, Br-, I-, SCN-, N3 -, NO3 -) have been synthesized and characterized by physical and spectral (FT/IR, UV-Vis, Mass, and 1H, 13C NMR spectroscopies) methods. Also nano-structured cadmium chloride and bromide complexes were synthesized by sonochemical method and then used to prepare nanostructured cadmium oxide confirmed by XRD and SEM techniques. Thermal behavior of the compounds was studied in the temperature range of 25 to 900 °C under N2 atmosphere at a heating rate of 20 °C/ min. Moreover, thermo-kinetic activation parameters of thermal decomposition steps were calculated according to the Coats-Redfern relationship. Antimicrobial activities of the synthesized compounds against two gram-positive and two gram-negative bacteria such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and two fungi of Candida albicans and Aspergillus niger were investigated by well diffusion method. SEM technique was used to monitor the morphological changes of the bacteria treated with the compounds. The 2,2-Diphenyl-1-picrylhydrazyl(DPPH) and the ferric reducing antioxidant power (FRAP) methods were used to evaluate the antioxidant ability of the ligand and its cadmium(II) complexes. In final, the cytotoxicity properties of the ligand and some cadmium(II) complexes against PC3 cancer cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) bioassay and nitric oxide (NO) level measurement. The morphological changes of prostate cancer (PC3) cells due to treatment with the ligand and its complexes confirmed their anticancer effectiveness.

Facile and Novel Synthetic Approach, Molecular Docking, Molecular Dynamics, and Drug-Likeness Evaluation of 9-Substituted Acridine Derivatives as Dual Anticancer and Antimicrobial Agents.

In the present study, numerous acridine derivatives A1-A20 were synthesized via aromatic nucleophilic substitution (SNAr) reaction of 9-chloroacridine with carbonyl hydrazides, amines, or phenolic derivatives depending upon facile, novel, and eco-friendly approaches (Microwave and ultrasonication assisted synthesis). The structures of the new compounds were elucidated using spectroscopic methods. The title products were assessed for their antimicrobial, antioxidant, and antiproliferative activities using numerous assays. Promisingly, the investigated compounds mainstream revealed promising antibacterial and anticancer activities. Thereafter, the investigated compounds' expected mode of action was debated by using an array of in silico studies. Compounds A2 and A3 were the most promising antimicrobial agents, while compounds A2, A5, and A7 revealed the most cytotoxic activities. Accordingly, RMSD, RMSF, Rg, and SASA analyses of compounds A2 and A3 were performed, and MMPBSA was calculated. Lastly, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyses of the novel acridine derivatives were investigated. The tested compounds' existing screening results afford an inspiring basis leading to developing new compelling antimicrobial and anticancer agents based on the acridine scaffold.

New 1H-1,2,4-Triazolyl Derivatives as Antimicrobial Agents.

New 1H-1,2,4-triazolyl derivatives were synthesized, and six of them were selected based on docking prediction for the investigation of their antimicrobial activity against five bacterial and eight fungal strains. All compounds demonstrated antibacterial activity with MIC lower than that of the ampicillin and chloramphenicol. In general, the most sensitive bacteria appeared to be P. fluorescens, while the plant pathogen X. campestris was the most resistant. The antifungal activity of the compounds was much better than the antibacterial activity. All compounds were more potent (6 to 45 times) than reference drugs ketoconazole and bifonazole with the best activity achieved by compound 4 a. A. versicolor, A. ochraceus, A.niger, and T.viride showed the highest sensitivity to compound 4 b, while, T. viride, P. funiculosum, and P.ochrochloron showed good sensitivity to compound 4 a. Molecular docking studies suggest that the probable mechanism of antibacterial activity involves the inhibition of the MurB enzyme of E. coli, while CYP51 of C. albicans appears to be involved in the mechanism of antifungal activity. It is worth mentioning that none of the tested compounds violated Lipinski's rule of five.

1D and 2D Coordination Polymers of Calcium with Nonsteroidal Anti-Inflammatory Drugs: Synthesis, Crystal Structures, Hirshfeld Surfaces, Antimicrobial and Antioxidant Activities.

Four alkaline earth metal complexes of ketoprofen (Hket) and indomethacin (Hind) were synthesized and characterized: [Ca(ket)2(H2O)2]n (1), [Mg(ket)2(H2O)2] (2), [Ca(ind)2(EtOH)2]n (3), and [Mg(ind)2(EtOH)2] (4). All compounds were studied by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Crystal structures of 1 and 3 were determined by single crystal X-ray diffraction technique T=100 K. The structure of 1 is dominated by a one-dimensional coordination polymer, while 3 is formed by a two-dimensional layer stabilized by the calcium zig-zag chains and π⋅⋅⋅π stacking interactions. Crystal packing arrangements were characterized by fingerprint plots (FPs) that were derived from the Hirshfeld surfaces (HSs). The antioxidant and antimicrobial activities of complexes were evaluated against Gram-positive and Gram-negative bacteria as well as yeasts.

Effect of Amino Acid Types on the Mechanical and Antimicrobial Properties of Amino Acid-Based Polyionic Liquid Hydrogels.

Polyionic liquid hydrogels attract increasing attention due to their unique properties and potential applications. However, research on amino acid-based polyionic liquid hydrogels is still in its infancy stage. Moreover, the effect of amino acid types on the properties of hydrogels is rarely studied to date. In this work, amino acid-based polyionic liquid hydrogels (D/L-PCAA hydrogels) are synthesized by copolymerizing vinyl choline-amino acid ionic liquids and acrylic acids using Al3+ as a crosslinking agent and bacterial cellulose (BC) as a reinforcing agent. The effects of amino acid types on mechanical and antimicrobial properties are systematically investigated. D-arginine-based hydrogel (D-PCArg) shows the highest tensile strength (220.7 KPa), D-phenylalanine-based hydrogel (D-PCPhe) exhibits the highest elongation at break (1346%), and L-aspartic acid-based hydrogel (L-PCAsp) has the highest elastic modulus (206.9 KPa) and toughness (1.74 MJ m-3). D/L-PCAsp hydrogels demonstrate stronger antibacterial capacity against Escherichia coli and Staphylococcus aureus, and D/L-PCPhe hydrogels possess higher antifungal activity against Cryptococcus neoformans. Moreover, the resultant hydrogels exhibit prominent hemocompatibility and low toxicity, as well as excellent self-healing capabilities (86%) and conductivity (2.8 S m-1). These results indicate that D/L-PCAA hydrogel provides a promise for applications in wound dressings.

Biological investigation of N-methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors.

The enormous burden of the COVID-19 pandemic in economic and healthcare terms has cast a shadow on the serious threat of antimicrobial resistance, increasing the inappropriate use of antibiotics and shifting the focus of drug discovery programmes from antibacterial and antifungal fields. Thus, there is a pressing need for new antimicrobials involving innovative modes of action (MoAs) to avoid cross-resistance rise. Thiosemicarbazones (TSCs) stand out due to their easy preparation and polypharmacological application, also in infectious diseases. Recently, we reported a small library of TSCs (1-9) that emerged for their non-cytotoxic behaviour. Inspired by their multifaceted activity, we investigated the antibacterial, antifungal, and antidermatophytal profiles of derivatives 1-9, highlighting a new promising research line. Furthermore, the ability of these compounds to inhibit selected microbial and human carbonic anhydrases (CAs) was assessed, revealing their possible involvement in the MoA and a good selectivity index for some derivatives.

Synthesis and Antimicrobial, Anticancer and Anti-Oxidant Activities of Novel 2,3-Dihydropyrido[2,3-d]pyrimidine-4-one and Pyrrolo[2,1-b][1,3]benzothiazole Derivatives via Microwave-Assisted Synthesis.

In our attempt towards the synthesis and development of effective antimicrobial, anticancer and antioxidant agents, a novel series of 2,3-dihydropyrido[2,3-d]pyrimidin-4-one 7a-e and pyrrolo[2,1-b][1,3]benzothiazoles 9a-e were synthesized. The synthesis of 2-(1,3-benzo thiazol-2-yl)-3-(aryl)prop-2-enenitrile (5a-e) as the key intermediate was accomplished by a microwave efficient method. Via a new variety oriented synthetic microwave pathway, these highly functionalized building blocks allowed access to numerous fused heteroaromatic such as 7-amino-6-(1,3-benzo thiazol-2-yl)-5-(aryl)-2-thioxo-2,3dihydropyrido [2,3-d]pyrimidin-4(1H)-one 7a-e and 1-amino-2-(aryl)pyrrolo[2,1-b][1,3]benzothiazole-3-carbonitrile derivatives 9a-e in order to study their antimicrobial and anticancer activity. The present investigation offers effective and rapid new procedures for the synthesis of the newly polycondensed heterocyclic ring systems. All the newly synthesized compounds were evaluated for antimicrobial, anticancer and antioxidant activity. Compounds 7a,d, and 9a,d showed higher antimicrobial activity than cefotaxime and fluconazole while the remaining compounds exhibited good to moderate activity against bacteria and fungi. An anticancer evaluation of the newly synthesized compounds against the three tumor cell lines (lung cell NCI-H460, liver cancer HepG2 and colon cancer HCT-116) exhibited that compounds 7a, d, and 9a,d have higher cytotoxicity against the three human cell lines compared to doxorubicin as a reference drug. These compounds also exhibited higher antioxidant activity and a great ability to protect DNA from damage induced by bleomycin.

Synthesis, Characterization, Biological Evaluation and DNA Interaction Studies of 4-Aminophenol Derivatives: Theoretical and Experimental Approach.

In the present study, five 4-aminophenol derivatives (4-chloro-2-(((4-hydroxyphenyl)imino)methyl)phenol(S-1), 4-((4-(dimethylamino)benzylidene)amino)phenol(S-2), 4-((3-nitrobenzylidene)amino)phenol(S-3), 4-((thiophen-2-ylmethylene)amino)phenol(S-4) and 4-(((E)-3-phenylallylidene)amino)phenol(S-5)) were synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR and elemental analyses. The synthesized compounds were tested for their antimicrobial (Gram-positive and Gram-negative bacteria and Saccharomyces cervesea fungus) and antidiabetic (α-amylase and α-glucosidase inhibitory) activities. All the compounds showed broad-spectrum activities against the Staphylococcus aureus (ATCC 6538), Micrococcus luteus (ATCC 4698), Staphylococcus epidermidis (ATCC 12228), Bacillus subtilis sub. sp spizizenii (ATCC 6633), Bordetella bronchiseptica (ATCC 4617) and Saccharomyces cerevisiae (ATCC 9763) strains. The newly synthesized compounds showed a significant inhibition of amylase (93.2%) and glucosidase (73.7%) in a concentration-dependent manner. Interaction studies of Human DNA with the synthesized Schiff bases were also performed. The spectral bands of S-1, S-2, S-3 and S-5 all showed hyperchromism, whereas the spectral band of S-4 showed a hypochromic effect. Moreover, the spectral bands of the S-2, S-3 and S-4 compounds were also found to exhibit a bathochromic shift (red shift). The present studies delineate broad-spectrum antimicrobial and antidiabetic activities of the synthesized compounds. Additionally, DNA interaction studies highlight the potential of synthetic compounds as anticancer agents. The DNA interaction studies, as well as the antidiabetic activities articulated by the molecular docking methods, showed the promising aspects of synthetic compounds.

Synthesis of Copper Oxide-Based Nanoformulations of Etoricoxib and Montelukast and Their Evaluation through Analgesic, Anti-Inflammatory, Anti-Pyretic, and Acute Toxicity Activities.

Copper oxide nanoparticles (CuO NPs) were synthesized through the coprecipitation method and used as nanocarriers for etoricoxib (selective COX-2 inhibitor drug) and montelukast (leukotriene product inhibitor drug) in combination therapy. The CuO NPs, free drugs, and nanoformulations were investigated through UV/Vis spectroscopy, FTIR spectroscopy, XRD, SEM, and DLS. SEM imaging showed agglomerated nanorods of CuO NPs of about 87 nm size. The CE1, CE2, and CE6 nanoformulations were investigated through DLS, and their particle sizes were 271, 258, and 254 nm, respectively. The nanoformulations were evaluated through in vitro anti-inflammatory activity, in vivo anti-inflammatory activity, in vivo analgesic activity, in vivo anti-pyretic activity, and in vivo acute toxicity activity. In vivo activities were performed on albino mice. BSA denaturation was highly inhibited by CE1, CE2, and CE6 as compared to other nanoformulations in the in vitro anti-inflammatory activity. The in vivo bioactivities showed that low doses (5 mg/kg) of nanoformulations were more potent than high doses (10 and 20 mg/kg) of free drugs in the inhibition of pain, fever, and inflammation. Lastly, CE2 was more potent than that of other nanoformulations.

N-((1H-Pyrrol-2-yl)methylene)-6-methoxypyridin-3-amine and Its Co(II) and Cu(II) Complexes as Antimicrobial Agents: Chemical Preparation, In Vitro Antimicrobial Evaluation, In Silico Analysis and Computational and Theoretical Chemistry Investigations.

Researchers are interested in Schiff bases and their metal complexes because they offer a wide range of applications. The chemistry of Schiff bases of heterocompounds has got a lot of attention because of the metal's ability to coordinate with Schiff base ligands. In the current study, a new bidentate Schiff base ligand, N-((1H-pyrrol-2-yl)methylene)-6-methoxypyridin-3-amine (MPM) has been synthesized by condensing 6-methoxypyridine-3-amine with pyrrole-2-carbaldehyde. Further, MPM is used to prepare Cu(II) and Co(II) metal complexes. Analytical and spectroscopic techniques are used for the structural elucidation of the synthesized compounds. Both MPM and its metal complexes were screened against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Klebsiella pneumoniae species for antimicrobial studies. Furthermore, these compounds were subjected to in silico studies against bacterial proteins to comprehend their best non-bonded interactions. The results confirmed that the Schiff base ligand show considerably higher binding affinity with good hydrogen bonding and hydrophobic interactions against various tested microbial species. These results were complemented with a report of the Conceptual DFT global reactivity descriptors of the studied compounds together with their biological scores and their ADMET computed parameters.