Facile Synthesis of 5-Bromo-N-Alkylthiophene-2-Sulfonamides and Its Activities Against Clinically Isolated New Delhi Metallo-ß-Lactamase Producing Klebsiella pneumoniae ST147.

Introduction: New Delhi Metallo-ß-lactamase producing Klebsiella pneumoniae (NDM-1-KP) sequence type (ST) 147 poses a significant threat in clinical settings due to its evolution into two distinct directions: hypervirulence and carbapenem resistance. Hypervirulence results from a range of virulence factors, while carbapenem resistance stems from complex biological mechanisms. The NDM-1-KP ST147 clone has emerged as a recent addition to the family of successful clones within the species. Methods: In this study, we successfully synthesized 5-bromo-N-alkylthiophene-2-sulfonamides (3a-c) by reacting 5-bromothiophene-2-sulfonamide (1) with various alkyl bromides (2) using LiH. We also synthesized a series of compounds (4a-g) from compound (3b) using the Suzuki-Miyaura cross-coupling reaction with fair to good yields (56-72%). Further, we screened the synthesized molecules against clinically isolated New Delhi Metallo-ß-lactamase producing Klebsiella pneumoniae ST147. Subsequently, we conducted in-silico tests on compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I. Results: The compound (3b) with favourable drug candidate status, MIC of 0.39 µg/mL, and MBC of 0.78 µg/mL. This low molecular weight compound exhibited the highest potency against the resistant bacterial strains. The in-silico tests revealed that the compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I demonstrated H-bond and hydrophobic interactions. Conclusion: The 5-bromo-N-alkylthiophene-2-sulfonamides displayed antibacterial efficacy against New Delhi Metallo-ß-lactamase producing Klebsiella pneumoniae ST147. After the in-vivo trial, this substance might offer an alternative therapeutic option.

Synthesis of 2-Ethylhexyl 5-Bromothiophene-2-Carboxylates; Antibacterial Activities against Salmonella Typhi, Validation via Docking Studies, Pharmacokinetics, and Structural Features Determination through DFT.

A new class of thiophene-based molecules of 5-bromothiophene-2-carboxylic acid (1) have been synthesized in current research work. All analogs 4A-4G were synthesized with optimized conditions by coupling reactions of 2-ethylhexyl 5-bromothiophene-2-carboxylate (3) with various arylboronic acids. The results indicated that the majority of compounds showed promising effective in vitro antibacterial activity. Herein, 2-ethylhexyl-5-(p-tolyl)thiophene-2-carboxylate (4F), in particular among the synthesized analogs, showed outstanding antibacterial action (MIC value 3.125 mg/mL) against XDR Salmonella Typhi compared to ciprofloxacin and ceftriaxone. The intermolecular interaction was investigated by using a molecular docking study of thiophene derivatives 4A-4G against XDR S. Typhi. The values of the binding affinity of functionalized thiophene molecules and ciprofloxacin were compared against bacterial enzyme PDB ID: 5ztj. Therefore, 4F appears to be a promising antibacterial agent and showed the highest potential value. Density functional theory (DFT) calculations were executed to examine the electronic, structural, and spectroscopic features of the newly synthesized molecules 4A-4G.

N-Heterocycles as Promising Antiviral Agents: A Comprehensive Overview.

Viruses are a real threat to every organism at any stage of life leading to extensive infections and casualties. N-heterocycles can affect the viral life cycle at many points, including viral entrance into host cells, viral genome replication, and the production of novel viral species. Certain N-heterocycles can also stimulate the host's immune system, producing antiviral cytokines and chemokines that can stop the reproduction of viruses. This review focused on recent five- or six-membered synthetic N-heterocyclic molecules showing antiviral activity through SAR analyses. The review will assist in identifying robust scaffolds that might be utilized to create effective antiviral drugs with either no or few side effects.

First-Principles Investigations of Novel Guanidine-Based Dyes.

In the pursuit of finding efficient D-π-A organic dyes as photosensitizers for dye-sensitized solar cells (DSSCs), first-principles calculations of guanidine-based dyes [A1-A18] were executed using density functional theory (DFT). The various electronic and optical properties of guanidine-based organic dyes with different D-π-A structural modifications were investigated. The structural modification of guanidine-based dyes largely affects the properties of molecules, such as excitation energies, the oscillator strength dipole moment, the transition dipole moment, and light-harvesting efficiencies. The energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) is responsible for the reduction and injection of electrons. Modification of the guanidine subunit by different structural modifications gave a range of HOMO-LUMO energy gaps. Chemical and optical characteristics of the dyes indicated prominent charge transfer and light-harvesting efficiencies. The wide electronic absorption spectra of these guanidine-based dyes computed by TD-DFT-B3LYP with 6-31G, 6-311G, and cc-PVDZ basis sets have been observed in the visible region of spectra due to the presence of chromophore groups of dye molecules. Better anchorage of dyes to the surface of TiO2 semiconductors helps in charge-transfer phenomena, and the results suggested that -COOH, -CN, and -NO2 proved to be proficient anchoring groups, making dyes very encouraging candidates for DSSCs. Molecular electrostatic potential explained the electrostatic potential of organic dyes, and IR spectrum and conformational analyses ensured the suitability of organic dyes for the fabrication of DSSCs.

Synthesis of anti-depressant molecules via metal-catalyzed reactions: a review.

Depression is one of the most mutilating conditions in the world today. It has been difficult to make advancements toward better, more effective therapies since the introduction of antidepressant medicines in the late 1950s. One important field of medicinal chemistry is the synthesis of antidepressant molecules through metal-catalyzed procedures. The important role that different transition metals, including iron, nickel, ruthenium, and others, serve as catalysts in the synthesis of antidepressants is examined in this review. Key structural motifs included in antidepressant drugs such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and others can be synthesized in a variety of effective ways using metal-catalyzed steps. This review examines current developments in the catalytic synthesis of antidepressants and their potential application over the previous thirteen years.

Dinuclear Zn-Catalytic System as Brønsted Base and Lewis Acid for Enantioselectivity in Same Chiral Environment.

Zinc (Zn) is a crucial element with remarkable significance in organic transformations. The profusion of harmless zinc salts in the Earth's outer layer qualifies zinc as a noteworthy contender for inexpensive and eco-friendly reagents and catalysts. Recently, widely recognized uses of organo-Zn compounds in the field of organic synthesis have undergone extensive expansion toward asymmetric transformations. The ProPhenol ligand, a member of the chiral nitrogenous-crown family, exhibits the spontaneous formation of a dual-metal complex when reacted with alkyl metal (R-M) reagents, e.g., ZnEt2. The afforded Zn complex possesses two active sites, one Lewis acid and the other Brønsted base, thereby facilitating the activation of nucleophiles and electrophiles simultaneously within the same chiral pocket. In this comprehensive analysis, we provide a thorough account of the advancement and synthetic potential of these diverse catalysts in organic synthesis, while emphasizing the reactivity and selectivities, i.e., dr and ee due to the design/structure of the ligands employed.

Synthesis of 1-(4-Bromobenzoyl)-1,3-dicyclohexylurea and Its Arylation via Readily Available Palladium Catalyst-Their Electronic, Spectroscopic, and Nonlinear Optical Studies via a Computational Approach.

In this study, we reported the synthesis of 1-(4-bromobenzoyl)-1,3-dicyclohexylurea by the reaction of DCC (N,N'-dicyclohexylcarbodiimide) with 4-bromobenzoic acid. Subsequently, we further synthesized a new series of 1-(4-arylbenzoyl)-1,3-dicyclohexylurea (5a-g) derivatives using a Suzuki cross-coupling reaction between 1-(4-bromobenzoyl)-1,3-dicyclohexylurea (3) and various aryl/heteroaryl boronic acids (4). Thus, density functional theory (DFT) calculations have been performed to examine the electronic structure of the synthesized compounds (3, 5a-g) and to calculate their spectroscopic data. Moreover, optimized geometries and thermodynamic properties, such as frontier molecular orbitals (HOMO, LUMO), molecular electrostatic potential surfaces, and reactivity descriptors, were also calculated at the PBE0-D3BJ/def2-TZVP/SMD1,4-dioxane level of theory to validate the structures of the synthesized compounds.

Synthesis, Anti-Bacterial and Molecular Docking Studies of Arylated Butyl 2-Bromoisonicotinate Against Clinical Isolates of ESBL-Producing Escherichia coli ST405 and Methicillin-Resistant Staphylococcus aureus.

Introduction: Global public health concerns include the emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase Escherichia coli (ESBL-E. coli). These pathogens cause infections that are difficult to treat, which can have fatal outcomes and require lengthy hospital stays. As a result, we created butyl 2-bromoisonicotinate and tested its antibacterial effectiveness against the ESBL-E. coli ST 405 and MRSA pathogens. Natural product discovery is complemented by synthetic compound synthesis because of the latter's potential for superior characteristics, target specificity, scalability, intellectual advantages, and chemical diversity. Because of this, the potential for discovering new medicinal compounds is increased, and the constraints placed on natural sources are overcome. Natural items are tough to obtain since they are hard to isolate and synthesize. Therefore, modern science is actively searching for small molecules as therapeutic agents by applying sustainable techniques that can be commercialized. Methods: Two patients' blood samples were taken, and the BACTEC/Alert system was used to process them. On blood and MacConkey agar, the positive samples were subcultured and incubated aerobically at 37 °C. Using the VITEK 2 compact system, the isolates were subjected to isolate identification and MIC. MLST of the ESBL-E. coli was performed by PCR. Additionally, Fischer esterification was used to create butyl 2-bromoisonicotinate in excellent yields. A commercially available palladium catalyst was then used to arylate the compound, resulting in medium to good yields of arylated butyl 2-bromoisonicotinates. Using the agar well diffusion assay and the micro-broth dilution method, we assessed the in-vitro activities of the synthesized molecules (3, 5a-h) against clinically isolated ESBL-E. coli ST405, and MRSA. A molecular operating environment was used to carry out in silico validation of the synthesized compounds' binding to the active site and to evaluate the stability of their molecular interactions with the target E. coli 2Y2T protein. Results: MRSA and ESBL-producing E. coli were identified as the two clinical isolates. While MRSA was also resistant to beta-lactam drugs and least resistant to vancomycin, ESBL-producing E. coli belonged to ST405 and was resistant to cephalosporins and sensitive to carbapenems. Good yields of the desired compounds were produced by our effective and economical synthesis. By using a micro-broth dilution assay, the Molecules (3, 5a, and 5d) were most effective against both resistant strains. The Molecules (3, 5a, 5b, and 5d) also displayed good binding energies. Conclusion: The butyl 2-bromoisonicotinate displayed antibacterial efficacy against ESBL-producing E. coli ST405 and MRSA strains. After the in-vivo trial, this substance might offer an alternative therapeutic option.

Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line.

Triazole-based acetamides serve as important scaffolds for various pharmacologically active drugs. In the present work, structural hybrids of 1,2,4-triazole and acetamides were furnished by chemically modifying 2-(4-isobutylphenyl) propanoic acid (1). Target compounds 7a-f were produced in considerable yields (70-76%) by coupling the triazole of compound 1 with different electrophiles under different reaction conditions. These triazole-coupled acetamide derivatives were verified by physiochemical and spectroscopic (HRMS, FTIR, 13CNMR, and 1HNMR,) methods. The anti-liver carcinoma effects of all of the derivatives against a HepG2 cell line were investigated. Compound 7f, with two methyl moieties at the ortho-position, exhibited the highest anti-proliferative activity among all of the compounds with an IC50 value of 16.782 µg/mL. 7f, the most effective anti-cancer molecule, also had a very low toxicity of 1.190.02%. Molecular docking demonstrates that all of the compounds, especially 7f, have exhibited excellent binding affinities of -176.749 kcal/mol and -170.066 kcal/mol to c-kit tyrosine kinase and protein kinase B, respectively. Compound 7f is recognized as the most suitable drug pharmacophore for the treatment of hepatocellular carcinoma.

Synergistic Antibacterial Screening of Cymbopogon citratus and Azadirachta indica: Phytochemical Profiling and Antioxidant and Hemolytic Activities.

Current studies were performed to investigate the phytochemistry, synergistic antibacterial, antioxidant, and hemolytic activities of ethanolic and aqueous extracts of Azadirachta indica (EA and WA) and Cymbopogon citratus (EC and WC) leaves. Fourier transform infrared data verified the existence of alcoholic, carboxylic, aldehydic, phenyl, and bromo moieties in plant leaves. The ethanolic extracts (EA and EC) were significantly richer in phenolics and flavonoids as compared to the aqueous extracts (WA and WC). The ethanolic extract of C. citratus (EC) contained higher concentrations of caffeic acid (1.432 mg/g), synapic acid (6.743 mg/g), and benzoic acid (7.431 mg/g) as compared to all other extracts, whereas chlorogenic acid (0.311 mg/g) was present only in the aqueous extract of A. indica (WA). Food preservative properties of C. citratus can be due to the presence of benzoic acid (7.431 mg/g). -Gas chromatography-mass spectrometry analysis demonstrated the presence of 36 and 23 compounds in A. indica and C. citratus leaves, respectively. Inductively coupled plasma analysis was used to determine the concentration of 26 metals (Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, Pb, Sb, Se, Si, Sn, Sr, V, Zn, Zr, Ti); the metal concentrations were higher in aqueous extracts as compared to the ethanolic extracts. The extracts were generally richer in calcium (3000-7858 ppm), potassium (13662-53,750 ppm), and sodium (3181-8445 ppm) and hence can be used in food supplements as a source of these metals. Antioxidant potential (DDPH method) of C. citratus ethanolic extract was the highest (74.50 ± 0.66%), whereas it was the lowest (32.22 ± 0.28%) for the aqueous extract of A. indica. Synergistic inhibition of bacteria (Staphylococcus aureus and Escherichia coli) was observed when the aqueous extracts of both the plants were mixed together in certain ratios (v/v). The highest antibacterial potential was exhibited by the pure extract of C. citratus, which was even higher than that of the standard drug (ciprofloxacin). The plant extracts and their mixtures were more active against S. aureus as compared to E. coli. No toxic hemolytic effects were observed for the investigated extracts indicating their safe medicinal uses for human beings.

Antibacterial Efficacy of N-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide Analogues against Extended-Spectrum-ß-Lactamase Producing Clinical Strain of Escherichia coli ST 131.

Development in the fields of natural-product-derived and synthetic small molecules is in stark contrast to the ongoing demand for novel antimicrobials to treat life-threatening infections caused by extended-spectrum ß-lactamase producing Escherichia coli (ESBL E. coli). Therefore, there is an interest in the antibacterial activities of synthesized N-(4-methylpyridin-2-yl) thiophene-2-carboxamides (4a-h) against ESBL-producing E. coli ST131 strains. A blood sample was obtained from a suspected septicemia patient and processed in the Bactec Alert system. The isolate's identification and antibacterial profile were determined using the VITEK 2® compact system. Multi-locus sequence typing of E. coli was conducted by identifying housekeeping genes, while ESBL phenotype detection was performed according to CLSI guidelines. Additionally, PCR was carried out to detect the blaCTX-M gene molecularly. Moreover, molecular docking studies of synthesized compounds (4a-h) demonstrated the binding pocket residues involved in the active site of the ß-lactamase receptor of E. coli. The result confirmed the detection of E. coli ST131 from septicemia patients. The isolates were identified as ESBL producers carrying the blaCTX-M gene, which provided resistance against cephalosporins and beta-lactam inhibitors but sensitivity to carbapenems. Among the compounds tested, 4a and 4c exhibited high activity and demonstrated the best fit and interactions with the binding pocket of the ß-lactamase enzyme. Interestingly, the maximum of the docking confirmations binds at a similar pocket region, further strengthening the importance of binding residues. Hence, the in vitro and molecular docking studies reflect the promising antibacterial effects of 4a and 4c compounds.

Antibacterial efficacy of indigenous Pakistani honey against extensively drug-resistant clinical isolates of Salmonella enterica serovar Typhi: an alternative option to combat antimicrobial resistance.

BACKGROUND: Extensively drug-resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) poses a grave threat to public health due to increased mortality and morbidity caused by typhoid fever. Honey is a promising antibacterial agent, and we aimed to determine the antibacterial activity of honey against XDR S. Typhi. METHODS: We isolated 20 clinical isolates of XDR S. Typhi from pediatric septicemic patients and determined the minimum inhibitory concentrations (MICs) of different antibiotics against the pathogens using the VITEK 2 Compact system. Antimicrobial-resistant genes carried by the isolates were identified using PCR. The antibacterial efficacy of five Pakistani honeys was examined using agar well diffusion assay, and their MICs and minimum bactericidal concentrations (MBCs) were determined with the broth microdilution method. RESULTS: All 20 isolates were confirmed as S. Typhi. The antibiogram phenotype was confirmed as XDR S. Typhi with resistance to ampicillin (≥ 32 µg/mL), ciprofloxacin (≥ 4 µg/mL), and ceftriaxone (≥ 4 µg/mL) and sensitivity to azithromycin (≤ 16 µg/mL) and carbapenems (≤ 1 µg/mL). Molecular conformation revealed the presence of blaTM-1, Sul1, qnrS, gyrA, gyrB, and blaCTX-M-15 genes in all isolates. Among the five honeys, beri honey had the highest zone of inhibition of 7-15 mm and neem honey had a zone of inhibition of 7-12 mm. The MIC and MBC of beri honey against 3/20 (15%) XDR S. Typhi isolates were 3.125 and 6.25%, respectively, while the MIC and MBC of neem were 3.125 and 6.25%, respectively, against 3/20 (15%) isolates and 6.25 and 12.5%, respectively, against 7/20 (35%) isolates. CONCLUSION: Indigenous honeys have an effective role in combating XDR S. Typhi. They are potential candidates for clinical trials as alternative therapeutic options against XDR S. Typhi isolates.

Anti-Diabetic and Cytotoxic Evaluation of Phlomis stewartii Plant Phytochemicals on Cigarette Smoke Inhalation and Alloxan-Induced Diabetes in Wistar Rats.

The generation of free radicals in body causes oxidative stress and consequently different metabolic disorders. There are numerous environmental and emotional factors that trigger free radical generation, cigarette smoke (CS) is one of them. In addition to free radical production, it also increases the risk of developing type II diabetes, cancer, and has adverse effects on other organs such as liver and kidneys. In the present study, extracts of leaves, flower, and whole plant of P. stewartii Hf. in methanol were analyzed using LC-ESI-MS and investigated for their cytotoxic properties against HepG2 cell line and CS alloxan-induced diabetes in Wistar albino rats model. A total of 24 rats were kept in aerated cage for eight weeks and exposed to CS following the administration of single dose of alloxan@140 mg/kg body weight at the end of six weeks to induce diabetes mellitus (DM). The cytotoxic activity of extracts against HepG2 was recorded in the order; leaves methanol (LM) > flower methanol (FM) and whole plant methanol (WPM). The IC50(1/4) values were in the order of 187 (LM) > 280 (FM) > 312 (WPM) µg/mL against HepG2. In positive control group, CS- and alloxan-induced diabetes significantly increased (p < 0.05) the level of alanine alkaline phosphatase (ALP), aminotransferase (ALT), aspartate aminotransferase (AST), low density lipoprotein (LDL), bilirubin, total protein, creatinine, uric acid, blood urea, globulin, total oxidant status (TOS), and malondialdehyde (MDA), as compared to negative control group. In conclusion, according to the results of this study, P. Stewartii methanol extracts showed good antioxidant, anticancer activity and worked well to recover the tested clinical parameters in CS/alloxan-induced diabetes animals, which indicated the extracts also possess good antidiabetic, hepatoprotective, and nephroprotective potential.

Total Synthesis of Terpenes and Their Biological Significance: A Critical Review.

Terpenes are a group of natural products made up of molecules with the formula (C5H8)n that are typically found in plants. They are widely employed in the medicinal, flavor, and fragrance industries. The total synthesis of terpenes as well as their origin and biological potential are discussed in this review.

Synthesis of Functionalized N-(4-Bromophenyl)furan-2-carboxamides via Suzuki-Miyaura Cross-Coupling: Anti-Bacterial Activities against Clinically Isolated Drug Resistant A. baumannii, K. pneumoniae, E. cloacae and MRSA and Its Validation via a Computational Approach.

N-(4-bromophenyl)furan-2-carboxamide (3) was synthesized by the reaction furan-2-carbonyl chloride (1) and 4-bromoaniline (2) in the presence of Et3N in excellent yields of 94%. The carboxamide (3) was arylated by employing triphenylphosphine palladium as a catalyst and K3PO4 as a base to afford N-(4-bromophenyl)furan-2-carboxamide analogues (5a-i) in moderate to good yields (43-83%). Furthermore, we investigated the in vitro anti-bacterial activities of the respective compounds against clinically isolated drug-resistant bacteria A. baumannii, K. pneumoniae, E. cloacae and S. aureus. The molecule (3) was found to be the most effective activity against these bacteria, particularly NDM-positive bacteria A. baumannii as compared to various commercially available drugs. Docking studies and MD simulations further validated it, expressing the active site and molecular interaction stability.

Facile Synthesis of Functionalized Phenoxy Quinolines: Antibacterial Activities against ESBL Producing Escherichia coli and MRSA, Docking Studies, and Structural Features Determination through Computational Approach.

The synthesis of new 6-Bromoquinolin-4-ol derivatives (3a-3h) by Chan-Lam coupling utilizing different types of solvents (protic, aprotic, and mixed solvents) and bases was studied in the present manuscript. Furthermore, their potential against ESBL producing Escherichia coli (ESBL E. coli) and methicillin-resistant Staphylococcusaureus (MRSA) were investigated. Commercially available 6-bromoquinolin-4-ol (3a) was reacted with different types of aryl boronic acids along with Cu(OAc)2 via Chan-Lam coupling methodology utilizing the protic and aprotic and mixed solvents. The molecules (3a-3h) exhibited very good yields with methanol, moderate yields with DMF, and low yields with ethanol solvents, while the mixed solvent CH3OH/H2O (8:1) gave more excellent results as compared to the other solvents. The in vitro antiseptic values against ESBL E. coli and MRSA were calculated at five different deliberations (10, 20, 30, 40, 50 mg/well) by agar well diffusion method. The molecule 3e depicted highest antibacterial activity while compounds 3b and 3d showed low antibacterial activity. Additionally, MIC and MBC standards were calculated against the established bacteria by broth dilution method. Furthermore, a molecular docking investigation of the derivatives (3a-3h) were performed. Compound (3e) was highly active and depicted the least binding energy of -5.4. Moreover, to investigate the essential structural and physical properties, the density functional theory (DFT) findings of the synthesized molecules were accomplished by using the basic set PBE0-D3BJ/def2-TZVP/SMD water level of the theory. The synthesized compounds showed an energy gap from 4.93 to 5.07 eV.

Synthesis of Functionalized Thiophene Based Pyrazole Amides via Various Catalytic Approaches: Structural Features through Computational Applications and Nonlinear Optical Properties.

In the present study, pyrazole-thiophene-based amide derivatives were synthesized by different methodologies. Here, 5-Bromothiophene carboxylic acid (2) was reacted with substituted, unsubstituted, and protected pyrazole to synthesize the amide. It was observed that unsubstituted amide (5-bromo-N-(5-methyl-1H-pyrazol-3-yl)thiophene-2-carboxamide (7) was obtained at a good yield of about 68 percent. The unsubstituted amide (7) was arylated through Pd (0)-catalyzed Suzuki-Miyaura cross-coupling, in the presence of tripotassium phosphate (K3PO4) as a base, and with 1,4-dioxane as a solvent. Moderate to good yields (66-81%) of newly synthesized derivatives were obtained. The geometry of the synthesized compounds (9a-9h) and other physical properties, like non-linear optical (NLO) properties, nuclear magnetic resonance (NMR), and other chemical reactivity descriptors, including the chemical hardness, electronic chemical potential, ionization potential, electron affinity, and electrophilicity index have also been calculated for the synthesized compounds. In this study, DFT calculations have been used to investigate the electronic structure of the synthesized compounds and to compute their NMR data. It was also observed that the computed NMR data manifested significant agreement with the experimental NMR results. Furthermore, compound (9f) exhibits a better non-linear optical response compared to all other compounds in the series. Based on frontier molecular orbital (FMO) analysis and the reactivity descriptors, compounds (9c) and (9h) were predicted to be the most chemically reactive, while (9d) was estimated to be the most stable among the examined series of compounds.

Recent trends in the chemistry of Sandmeyer reaction: a review.

Metal-catalyzed reactions play a vital part to construct a variety of pharmaceutically important scaffolds from past few decades. To carry out these reactions under mild conditions with low-cost easily available precursors, various new methodologies have been reported day by day. Sandmeyer reaction is one of these, first discovered by Sandmeyer in 1884. It is a well-known reaction mainly used for the conversion of an aryl amine to an aryl halide in the presence of Cu(I) halide via formation of diazonium salt intermediate. This reaction can be processed with or without copper catalysts for the formation of C-X (X = Cl, Br, I, etc.), C-CF3/CF2, C-CN, C-S, etc., linkages. As a result, corresponding aryl halides, trifluoromethylated compounds, aryl nitriles and aryl thioethers can be obtained which are effectively used for the construction of biologically active compounds. This review article discloses various literature reports about Sandmeyer-related transformations developed during 2000-2021 which give different ideas to synthetic chemists about further development of new and efficient protocols for Sandmeyer reaction. An updated compilation of new approaches for Sandmeyer reaction is described in this review to construct a variety of carbon-halogen, carbon-phosphorous, carbon-sulfur, carbon-boron etc. linkages.

N-([1,1'-biaryl]-4-yl)-1-naphthamide-based scaffolds synthesis, their cheminformatics analyses, and screening as bacterial biofilm inhibitor.

Naphthamides have pharmacological potential as they express strong activities against microorganisms. The commercially available naphthoyl chloride and 4-bromoaniline were condensed in dry dichloromethane (DCM) in the presence of Et3 N to form N-(4-bromophenyl)-1-naphthamide (86%) (3). Using a Pd(0) catalyzed Suzuki-Miyaura Cross-Coupling reaction of (3) and various boronic acids, a series of N-([1,1'-biaryl]-4-yl)-1-naphthamide derivatives (4a-h) were synthesized in moderate to good yields. The synthesized derivatives were evaluated for cytotoxicity haemolytic assay and biofilm inhibition activity through in silico and in vitro studies. Molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity risk, and other cheminformatics predict synthesized molecules as biologically active moieties, further validated through in vitro studies in which compounds (4c) and (4f) showed significant haemolytic activity whereas (4e) exhibited an efficient biofilm inhibition activity against Gram-negative bacteria Escherichia coli and Gram-positive bacteria Bacillus subtilis. When forming biofilms, bacteria become resistant to various antimicrobial treatments. Currently, research is focused on the development of agents that inhibit biofilm formation, thus the present work is valuable for preventing future drug resistance.

Facile Synthesis of 5-Aryl-N-(pyrazin-2-yl)thiophene-2-carboxamides via Suzuki Cross-Coupling Reactions, Their Electronic and Nonlinear Optical Properties through DFT Calculations.

Synthesis of 5-aryl-N-(pyrazin-2-yl)thiophene-2-carboxamides (4a-4n) by a Suzuki cross-coupling reaction of 5-bromo-N-(pyrazin-2-yl)thiophene-2-carboxamide (3) with various aryl/heteroaryl boronic acids/pinacol esters was observed in this article. The intermediate compound 3 was prepared by condensation of pyrazin-2-amine (1) with 5-bromothiophene-2-carboxylic acid (2) mediated by TiCl4. The target pyrazine analogs (4a-4n) were confirmed by NMR and mass spectrometry. In DFT calculation of target molecules, several reactivity parameters like FMOs (EHOMO, ELUMO), HOMO-LUMO energy gap, electron affinity (A), ionization energy (I), electrophilicity index (ω), chemical softness (σ) and chemical hardness (η) were considered and discussed. Effect of various substituents was observed on values of the HOMO-LUMO energy gap and hyperpolarizability. The p-electronic delocalization extended over pyrazine, benzene and thiophene was examined in studying the NLO behavior. The chemical shifts of 1H NMR of all the synthesized compounds 4a-4n were calculated and compared with the experimental values.