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In this paper, we reported the development of an efficient and highly productive synthetic protocol for preparing new 2,5-diamino-1,3,4-thiadiazole derivatives functionalized with N-(2,2,2-trichloroethyl)carboxamide group. The method of their preparation was based on the reaction of oxidative dehydrosulfurization of N-(2,2,2-trichloro-1-(2-(phenylcarbamothioyl)hydrazine-1-carbothioamido)ethyl)-carboxamides and N-(1-(2-carbamothioylhydrazine-1-carbothioamido)-2,2,2-trichloroethyl)benzamide under the action of a mixture of iodine and triethylamine in DMF. This reaction took place at room temperature for two hours and allowed obtaining the target products with a 69-75% yield. Using the developed protocol, we obtained ten new derivatives of 1,3,4-thiadiazole. Their structure was proven by IR,1H NMR,13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC spectroscopy, and LC/HRMS spectrometry. [ABSTRACT FROM AUTHOR]

This work focused on analyzing the properties of N‐(5‐nitrothiazol‐2‐yl)furan‐2‐carboxamide (C8H5N3O4S, NTFC) as a possible inhibitor of the rheumatoid arthritis process. The synthesis of NTFC was carried out and good‐quality crystals were obtained and studied by NMR (1H and 13C), DEPT 135, UV–Vis, IR, MS and single‐crystal X‐ray diffraction. The structure of NTFC consists of two rings, thiazole and furan, and a central C—N—C(=O)—C segment, which appears to be planar. This central amide segment forms angles of 2.61 (10) and 7.97 (11)° with the planes of the thiazole and furan rings, respectively. The crystal structure of NTFC exhibits N—H...N, N—H...O and C—H...O hydrogen bonds, and C—H...π and π–π interactions that facilitate self‐assembly and the formation of hydrogen‐bonded dimers, which implies the appearance of R22(8) graph‐set motifs in this interaction. The stability of the dimeric unit is complemented by the formation of strong intramolecular C—S...O interactions of chalcogen character, with an S...O distance of 2.6040 (18) Å. Hirshfeld surface (HS) analysis revealed that O...H/H...O interactions were dominant, accounting for 36.8% of the total HS, and that N—H...N interactions were fundamental to the formation of the dimeric structure. The molecular electrostatic potential (MEP) map showed a maximum energy of 46.73 kcal mol−1 and a minimum of −36.06 kcal mol−1. The interaction energies of molecular pairs around NTFC are highest for those interactions linked by N—H hydrogen bonds. The properties of the NTFC ligand as a potential inhibitor of the DHODH (dihydroorotate dehydrogenase) enzyme were evaluated by molecular docking, showing coupling energies very close to those obtained with the control drug for rheumatoid arthritis, i.e. leflunomide. [ABSTRACT FROM AUTHOR]

A series of new 5-(trifluoromethyl)-benzo[d]imidazole linked N-phenylamide compounds was designed and synthesized using 1-chloro-2-nitro-4-(trifluoromethyl)benzene as raw material via five steps. Their structures were confirmed by 1H NMR, 13C NMR and HRMS. The bioassay results indicated that some of them exhibited moderate insecticidal activity (>50% inhibition) against Mythimna separata and Nilaparvata lugens at 500 μg/mL. [ABSTRACT FROM AUTHOR]

AbstractThis paper describes the synthesis and in vitro biological evaluation of new compounds designated as 5(a-h) and 8(a-f). These compounds were synthesized by the reaction of thiazole derivative (3) or thiadiazole derivative (7) with urea and various aromatic aldehydes 4(a-h) in ethanol. The structures of the synthesized compounds were checked by IR,1H,13C NMR, and Mass spectroscopy. The antibacterial and antifungal activities of the compounds were evaluated against Escherichia coli (Gram-negative), Staphylococcus aureus (Gram-positive), and Candida albicans (fungus) using agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal/fungicidal concentration methods. The cytotoxic activities of these compounds against HT-29 and A-549 cancer cell lines were assessed in vitro by the MTT method. Our studies showed compounds 8c and 8f to have the most expressed antibacterial activity against S. aureus, while compounds 8c and 8d were the most potent against E. coli. Compounds 5h and 8e showed the highest antifungal activity against C. albicans, and compound 5f showed the most potent activity against the tested cancer cell lines. [ABSTRACT FROM AUTHOR]

Substituted furan carboxamide and Schiff base derivatives were evaluated for their hypolipidemic activity. Fourteen derivatives were synthesised: substituted-furan-2-carboxamides of acetophenones, anilines, and benzophenones a (1–8), furan-3-carboxamide (c1), and imines derivatives b (1–5). These compounds were synthesised, purified and fully characterised. All the new derivatives were verified in-vivo utilising Triton WR-1339 induced hyperlipidemic rats as animal model. The potential agents were administered via intraperitoneal injection of 20 mg/kg. Fenofibrate (with a dose 100 mg/kg, orally) was used in this research to validate the model. Remarkably, the new derivatives a (1–8), b (1–5) and c1 have shown significant effect against the whole lipid profile; by lowering the plasma triglyceride (TG), plasma total cholesterol (TC), low-density lipoprotein (LDL) level and elevating high-density lipoproteins (HDL) plasma levels comparing to the hyperlipidemic rats. The agents reduce TG with most significant results by (97%, 96%, 87% and 86%) relating to a1, a3, a8 and b5 respectively. Favourably, some of the proposed agents are more significant in reducing TG than fenofibrate. Some agents reduce LDL with most significant results by (76%, 72%, 60%, 60% and 60%) relating to a1, a3, a5, a8 and b5 respectively, and to a lower extent they increase HDL levels with most significant results by (75%, 64%, and 48%) for a1, a3, and a5 respectively. All the new derivatives were computationally docked at the hPPAR-α active site as possible target for these derivatives. The binding affinities were reported and showed good correlation to the in-vivo results as antihyperlipidemic agents. [ABSTRACT FROM AUTHOR]

Abstract In this work, a novel series of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives 5a–n were designed by consideration of the potent α-glucosidase inhibitors containing indole and carboxamide-1,2,3-triazole-N-phenylacetamide moieties. These compounds were synthesized by click reaction and evaluated against yeast α-glucosidase. All the newly title compounds demonstrated superior potency when compared with acarbose as a standard inhibitor. Particularly, compound 5k possessed the best inhibitory activity against α-glucosidase with around a 28-fold improvement in the inhibition effect in comparison standard inhibitor. This compound showed a competitive type of inhibition in the kinetics. The molecular docking and dynamics demonstrated that compound 5k with a favorable binding energy well occupied the active site of α-glucosidase.

Abstract Because of the great pharmacological and industrial significance of 1,3,4-thiadiazole and its related compounds, researchers are still very interested in them. For this reason, in this study, we looked at ways to create new hybrid compounds containing carboxamide and 1,3,4-thiadiazole moieties. The thioxoacetamide derivatives used to make these compounds were reacted with various alkylated reagents to produce multiple S-alkyl groups. Additionally, these compounds were reacted with aldehydes to form novel derivatives known as 5-(substituent)-N-phenyl-1,3,4-thiadiazole-2-carboxamide. Here, we used the agar well diffusion method to examine the antibacterial activity of all the produced compounds against a few pathogenic bacteria that were resistant to multiple drugs. Additionally, look into their capacity to lower inflammation through the use of bovine serum albumin in the protein denaturation procedure. The substances were characterized by spectral analysis (IR, 1HNMR, 13CNMR and Elemental Analysis), and efficient as antibacterial agents against all the tested bacterial strains, except for Escherichia coli. Compounds 4a and 8c showed the highest level of inhibition zone against Gram-positive bacteria (Staph. aureus, Bacillus subtilis) at concentration 0.3, 0.4 and 0.5 mg/ml compared with ciprofloxacin at the same concentrations. The results demonstrated that every compound has significant anti-inflammatory activity. At a concentration of 250 µg/ml, compounds 3a, 4c and 8c had the highest percentage inhibition of protein denaturation when (83.24%, 86.44% and 85.14%, respectively) compared to other compounds and diclofenac sodium as reference drug. Comparing compounds 4c and 8c to ciprofloxacin and diclofenac sodium, they showed powerful antibacterial and anti-inflammatory action. Furthermore, an investigation using molecular docking against DHPS from S. aureus (PDB ID: 6CLV) showed a strong connection with the intended protein and an elevated docking score, making it a prime candidate for antibiotics.

Because of the great pharmacological and industrial significance of 1,3,4-thiadiazole and its related compounds, researchers are still very interested in them. For this reason, in this study, we looked at ways to create new hybrid compounds containing carboxamide and 1,3,4-thiadiazole moieties. The thioxoacetamide derivatives used to make these compounds were reacted with various alkylated reagents to produce multiple S-alkyl groups. Additionally, these compounds were reacted with aldehydes to form novel derivatives known as 5-(substituent)-N-phenyl-1,3,4-thiadiazole-2-carboxamide. Here, we used the agar well diffusion method to examine the antibacterial activity of all the produced compounds against a few pathogenic bacteria that were resistant to multiple drugs. Additionally, look into their capacity to lower inflammation through the use of bovine serum albumin in the protein denaturation procedure. The substances were characterized by spectral analysis (IR, 1HNMR, 13CNMR and Elemental Analysis), and efficient as antibacterial agents against all the tested bacterial strains, except for Escherichia coli. Compounds 4a and 8c showed the highest level of inhibition zone against Gram-positive bacteria (Staph. aureus, Bacillus subtilis) at concentration 0.3, 0.4 and 0.5 mg/ml compared with ciprofloxacin at the same concentrations. The results demonstrated that every compound has significant anti-inflammatory activity. At a concentration of 250 µg/ml, compounds 3a, 4c and 8c had the highest percentage inhibition of protein denaturation when (83.24%, 86.44% and 85.14%, respectively) compared to other compounds and diclofenac sodium as reference drug. Comparing compounds 4c and 8c to ciprofloxacin and diclofenac sodium, they showed powerful antibacterial and anti-inflammatory action. Furthermore, an investigation using molecular docking against DHPS from S. aureus (PDB ID: 6CLV) showed a strong connection with the intended protein and an elevated docking score, making it a prime candidate for antibiotics. [ABSTRACT FROM AUTHOR]

An optimal balance between excitatory and inhibitory transmission in the central nervous system provides essential neurotransmission for good functioning of the neurons. In the neurology field, a disturbed balance can lead to neurological diseases like epilepsy, Alzheimer's, and Autism. One of the critical agents mediating excitatory neurotransmission is α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors, which are concerned with synaptic plasticity, memory, and learning. An imbalance in neurotransmission finally results in excitotoxicity and neurological pathologies that should be corrected through specific compounds. Hence, the current study will prove to be an evaluation of new thiazole-carboxamide derivatives concerning AMPAR-modulating activity and extended medicinal potential. In the current project, five previously synthesized thiazole-carboxamide derivatives, i.e., TC-1 to TC-5, were used to interact with the AMPARs expressed in HEK293T cells, which overexpress different subunits of the AMPAR. Patch-clamp analysis was carried out while the effect of the drugs on AMPAR-mediated currents was followed with a particular emphasis on the kinetics of inhibition, desensitization, and deactivation. All tested TC compounds, at all subunits, showed potent inhibition of AMPAR-mediated currents, with TC-2 being the most powerful for all subunits. These compounds shifted the receptor kinetics efficiently, mainly enhancing the deactivation rates, and hence acted as a surrogate for their neuroprotective potentials. Additionally, recently published structure–activity relationship studies identified particular substituent groups as necessary for improving the pharmacologic profiles of these compounds. In this regard, thiazole-carboxamide derivatives, particularly those classified as TC-2, have become essential negative allosteric modulators of AMPAR function and potential therapeutics in neurological disturbances underlain by the dysregulation of excitatory neurotransmission. Given their therapeutic effectiveness and safety profiles, these in vivo studies need to be further validated, although computational modeling can be further developed for drug design and selectivity. This will open possibilities for new drug-like AMPAR negative allosteric modulators with applications at the clinical level toward neurology. [ABSTRACT FROM AUTHOR]

A series of novel carboxamide compounds containing benzoxazole motif was synthesized through multiple steps, including electrophilic substitution, cyclization, reduction and amide formation. These processes utilized ortho-aminophenol and heptafluoro-2-iodopropane as starting materials. The structures of these compounds (4a–4r) were characterized by 1H NMR, 13C NMR, and HRMS. Bioassay results revealed that most of these compounds exhibited significant insecticidal activity against Mythimna separata at 500 mg/L. Among them, compound 6-chloro-N-(4-methoxy-3-(6-(perfluoropropan-2-yl)benzo[d]oxazol-2-yl)phenyl)-N-methylnicotinamide (4r) possessed the highest activity, even at 4 mg/L. Molecular docking predicted the binding modes of 4r. These novel carboxamide compounds containing benzoxazole motifs offer valuable insights for designing insecticidal compounds targeting GABA receptors, aiming to control lepidopteran pests effectively. [ABSTRACT FROM AUTHOR]

The rates of substitution of the chloride ligand in dinuclear complexes, [Pt2(N,N'-bis(2-pyridylcarboxamide)-1,3-phenylenediamine)Cl4] (1), [Pt2(N,N'-bis(2-pyridylcarboxamide)-1,4-phenylenediamine)Cl4] (2), [Pt2(N,N'-bis(3-isoquinolylcarboxamide)-1,3-phenylenediamine)Cl4] (3) and [Pt2(N,N'-bis(3-isoquinolylcarboxamide)-1,4-phenylenediamine)Cl4] (4), by three bio-relevant nucleophiles, thiourea (TU), N,N-dimethylthiourea (DMTU) and N,N,N',N'-tetramethylthiourea (TMTU), were investigated. The mononuclear analogue [Pt(N-phenylpyridine-2-carboxamide)Cl2] (5) was included to compare the results. The kinetics of the reactions were studied under pseudo first-order conditions in a methanol solution (I = 0.1 M LiCl) as a function of concentration and temperature using the stopped-flow spectrophotometer. The observed pseudo first-order rate constants for the substitution reactions of all the complexes were calculated from two well-separated steps and obey the rate law kobs (1st/2nd) = k2 (1st/2nd)[Nu]. The reactivity of the complexes decreases in the order 2 > 1 > 4 > 3 > 5. The conformational symmetry of the complexes as controlled by the phenylenediamine bridges, steric hindrance due to the bridges as well as the σ-donor capacity of the coordinated groups around the metal centers influence the reactivity of the dinuclear complexes. The low enthalpy (ΔH#) and negative intrinsic entropy (ΔS#) values support an associative mechanism of substitution. The kinetic data are supported by DFT calculations. [ABSTRACT FROM AUTHOR]

A new adeninecarboxamide ligand, N-(9 H-purin-6-yl) pyridine-2-carboxamide (H2pzac) has been synthesized by a green chemistry method using tetrabutylammunium bromide (TBAB) ionic liquid as an environmentally friendly reaction medium. The H2pzac ligand was anchored on modified SBA-15-Cl and utilized for detection of Hg2+ in aqueous solution. The as-constructed SBA-15@Hpzac sensor shows a high specific surface area as well as pore volume of 250 m2/g and 0.54 cm3/g, respectively. The fluorescence assessment indicated that the designed SBA-15@Hpzac sensor presented highly sensitive and selective behavior to Hg2+ ion over different cations including Zn2+, Ni2+, Co2+, Cu2+, Mn2+, Pb2+, Ba2+, Mg2+, Ca2+, Na+, Fe3+, Fe2+, Al3+, Cd2+ and K+. The fluorescence response of the SBA-15@Hpzac sensor for selective detection of Hg2+ ion is excellent with detection limit (LOD) of 1.07 × 10− 6 M. The application of the SBA-15@Hpzac sensor in determination of Hg2+ ions in two real water samples was also investigated. [ABSTRACT FROM AUTHOR]

Substituted cyclohexane derivatives are used as key compounds in the synthesis of different natural or synthetic compounds. In this context, we synthesized a new 1,6-disubstituted cyclohexene derivative and studied its bromination reaction. First, we obtained carboxamide 11 containing three functional groups by reduction of tetrahydro-1H-isoindole-1,3(2H)-dione with NaBH4. Bromination of carboxamide 11 gave the interesting rearrangement product hexa-hydroisobenzofuran-1(3H)iliden)methanaminium depending on the groups in the cyclohexene ring and its exact configuration was determined by X-ray analysis. Hydrolysis of the iminium salt gave 5-bromo-6-hydroxyhexyhexahydro isobenzofuran-1(3H)one. The reaction mechanism for the rearrangement product was proposed. As a result, two unexpected reactions occurred in the bromination reaction. The first is the incorporation of halohydrin into the molecule in anhydrous medium and the second is the facile formation of the five-membered lactone ring. [ABSTRACT FROM AUTHOR]

Laquinimod (ABR-215062) is a quinolone-3-carboxamide derivative, which is an orally active immunostimulatory drug molecule and is being developed for multiple sclerosis cases like relapsing-remitting multiple sclerosis (RRMS) and chronic progressive multiple sclerosis (CPMS). Laquinimod may mediate its effects by regulating pro-inflammatory immune responses and interfering with cell trafficking, in addition to possibly acting directly in the central nervous system to prevent demyelination and axonal injury. Nowadays, its benefits are extended further to various other neurodegenerative illnesses. Recently, it was found that laquinimod can exert only minimal effects in the clinical trials for both PPMS and RRMS making it not suitable for the treatment. However, cannot be completely neglected its pharmacological effect for curing disease progression in MS. Modification of the core structure can contribute to a better candidate for the treatment of MS. We have systematically reviewed the literature reported and highlighted the effect of laquinimod therapy not only on multiple sclerosis (MS) patients but also on a variety of other neurodegenerative disorders. Hence, this review can aid the research community in the design and development of novel chemical entities for the effective treatment of neurodegenerative disorders (NDDs).

A single-site Fe(III) carboxamide complex, [Fe(HbpH) (Cl) 2 ] (1), (HbpH‾ = N,N′-Bis(picolinoyl)hydrazine) anion), was synthesized and used as the electrocatalyst of water oxidation reaction. Complex 1 catalyzes the oxidation of water to O 2 at the pH of 8 in phosphate buffer solution with the onset of a catalytic wave at about 0.45 V versus RHE with the turnover frequency (TOF) of 5.8 s−1 at room temperature. The stability of the catalyst in water oxidation processes by electrochemical and UV–vis measurements, demonstrated the realistic molecular electrocatalysis of 1. Differential pulse voltammetry (DPV) of 1 in different pH values showed the dependency of oxidation potential to the pH of the environment, establishing the fact that the catalytic cycle involves the proton-coupled electron transfer (PCET) process. Density functional theory (DFT) calculations on the mechanism of water oxidation process of 1 shows that the oxygen evolution reaction is carried out through the water nucleophilic attack (WNA) to the metal center ion, resulted to the formation of FeIV(O) species. Also, DFT calculations showed that the formation of an O–O bond proceeds through the interaction two molecular mechanism (I2M), which compete with the WNA mechanism following from experimental analysis. The electroactivity of the metal centre and carboxamide ligand and the ability of the ligand to stabilize the high oxidation numbers of the metal-ion centre during the oxidation process, provide different oxidation pathways for an OER process. • Synthesis of carboxamide Fe(III) complex using ionic liquid as an environmentally benign reaction medium. • Electrocatalytic studies of the [Fe(HbpH) (Cl) 2 ] (1) in the OER process. • TOF values of 5.8 mol of hydrogen in each mole of catalyst per second for the catalyst 1. • The I2M mechanism competes with the WNA mechanism investigation using DFT calculations in OER process. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of mortality worldwide, making it a public health concern. A novel series of pyrrolidine‐carboxamide derivatives 7a‐q were developed and examined in a cell viability assay utilizing a human mammary gland epithelial cell line (MCF‐10A), where all the compounds exhibited no cytotoxic effects and more than 85% cell viability at a concentration of 50 μM. Antiproliferative activity was evaluated in vitro against four panels of cancer cell lines A‐549, MCF‐7, Panc‐1, and HT‐29. Compounds 7e, 7g, 7k, 7n, and 7o were the most active as antiproliferative agents capable of triggering apoptosis. Compound 7g was the most potent of all the derivatives, with a mean IC50 of 0.90 μM compared to IC50 of 1.10 μM for doxorubicin. Compound 7g inhibited A‐549 (epithelial cancer cell line), MCF‐7 (breast cancer cell line), and HT‐29 (colon cancer cell line) more efficiently than doxorubicin. EGFR inhibitory assay results of 7e, 7g, 7k, 7n, and 7o demonstrated that the tested compounds inhibited EGFR with IC50 values ranging from 87 to 107 nM in comparison with the reference drug erlotinib (IC50 = 80 nM). 7e, 7g, 7k, 7n, and 7o inhibited CDK2 efficiently in comparison to the reference dinaciclib (IC50 = 20 nM), with IC50 values ranging from 15 to 31 nM. The results of inhibitory activity assay against different CDK isoforms revealed that the tested compounds had preferential inhibitory activity against the CDK2 isoform. [ABSTRACT FROM AUTHOR]

Direct synthesis of Pyridine-2,6-dicarboxylic a-+cid bis-(3-hydroxy phenyl)]amide, (Pydca), chelating ligand was applied for Th(IV) extraction from Abu Rusheid Ore Sample, South Eastern Desert, Egypt, between latitudes 24° 37ʹ 16ʹʹ N and longitudes 34° 46 ʹ 35 ʹʹ E and far from the Red Sea coast by about 42 km west, using poly phosphoric acid catalyst (PPA). The synthesis of new amide via direct condensation of organic acid and aromatic amine was performed in DMF at 100°C. The immediate condensation reaction led to construct the carboxamide derivative in one easy step dismantling the hard activation, halogenation, step resulting in a good yield production. This cross-coupling reaction appears simple, convenient and has a wide scope of activities. This protocol could be extended to industrial large-scale production processes. Experimental measurements have been optimised such as diluent type, pH, contact time, initial Th(IV) concentration, temperature, pydca conc., co-existing ions and stripping agents. It was found that a maximum value of Th(IV) retention (0.86 × 10−3 mol/L) is observed with 0.015 mol/L pydca/CCl4 chelating ligand at room temperature. From kinetic aspects, it was found that Th(IV) extraction follows the pseudo-first order kinetic model. The thermodynamic parameters, ΔS, ΔH and ΔG were also evaluated indicating an endothermic and spontaneous extraction process with increasing the randomness of the extraction system. Th(IV) can be completely back extracted from the loaded pydca chelating ligand using 0.5 M HNO3, 1 M H2SO4 and 1 M HCl. Finally, the optimised factors have been applied for Th(IV) recovery from Abu Rusheid Ore Sample, South Eastern Desert, Egypt, producing a thorium oxide concentrate with Th(IV) content of 81.43% with a purity of 92.67%. [ABSTRACT FROM AUTHOR]

Reactions of ligand pyrazine‐2‐carboxylic acid (HL1) with [Ru(η6‐p‐cymene)Cl2]2 precursor gave the dinuclear piano‐stool ruthenium (II) complex [{Ru(η6‐p‐cymene)Cl2}‐μ‐(L1)‐{Ru(p‐cymene)Cl}] (Ru1). Separately, reactions of N‐(quinolin‐8‐yl) pyrazine‐2‐carboxamide (HL2), 5‐methyl‐N‐(−(quinolin‐8‐yl) pyridine‐2‐carboxamide (HL3) and 5‐chloro‐N‐(quinolin‐8‐yl) pyridine‐2‐carboxamide (HL4) with [Ru(η6‐p‐cymene)Cl2]2 dimer in the presence of KPF6 afforded the cationic dinuclear complexes [{Ru(η6‐p‐cymene)Cl}2‐μ‐(L2)][PF6] (Ru2), [{Ru(η6‐p‐cymene)Cl}2‐μ‐(L3)][Ru(L3)Cl3] (Ru3) and [{Ru(η6‐p‐cymene)Cl}2‐μ‐(L4)][PF6] (Ru4). The Ru (II) complexes were analysed using FT‐IR, 1H, 13C{1H}, 31P{1H} (Ru2 and Ru4) and 19F (Ru2 and Ru4) NMR spectroscopic techniques, micro‐analyses and mass spectrometry. Molecular structures of complexes Ru1 and Ru3 were confirmed to display piano‐stool coordination nature using single‐crystal X‐ray crystallography analyses. All the complexes (Ru1–Ru4) mediated the transfer hydrogenation (TH) of a broad spectrum of ketones in isopropanol in the presence of a base and demonstrated high catalytic activities (TON of 24,000) at catalyst concentrations of 0.002 mol%. In general, the catalytic performance of these Ru (II) complexes depended on the identity of the ligands, coordination chemistry and ketone substrates. [ABSTRACT FROM AUTHOR]

Naegleria fowleri is a free-living thermophilic flagellate amoeba that causes a rare but life-threatening infection called primary amoebic meningoencephalitis (PAM), with a very high fatality rate. Herein, the anti-amoebic potential of carboxamide derivatives possessing sulfonyl or sulfamoyl moiety was assessed against pathogenic N. fowleri using amoebicidal, cytotoxicity and cytopathogenicity assays. The results from amoebicidal experiments showed that derivatives dramatically reduced N. fowleri viability. Selected derivatives demonstrated IC50 values at lower concentrations; 1j showed IC50 at 24.65 μM, while 1k inhibited 50% amoebae growth at 23.31 μM. Compounds with significant amoebicidal effects demonstrated limited cytotoxicity against human cerebral microvascular endothelial cells. Finally, some derivatives mitigated N. fowleri-instigated host cell death. Ultimately, this study demonstrated that 1j and 1k exhibited potent anti-amoebic activity and ought to be looked at in future studies for the development of therapeutic anti-amoebic pharmaceuticals. Further investigation is required to determine the clinical relevance of our findings. [ABSTRACT FROM AUTHOR]

Sulfonamide-based carboxamide drugs have multiple active sites that confers them with a variety of chemical and pharmacological activities. The combination of structural functionalities has been established to be vital in the drug discovery process. The synthesis of novel, nontoxic, cheap and effective anti-parasitic analogues is a trending aspect of pharmaceutical and medicinal chemistry research. In this research, the synthesis, characterization, and density functional theory (DFT) investigation of the reactivity and anti-trypanosomal simulation of benzenesulphonamide-based carboxamide derivatives was carried out for 2-[N-(benzenesulfonyl)-1-phenylformamido]-N-(4-nitrophenyl)acetamide(BPNA), 2-[N-(benzenesulfonyl)-1-phenylformamido]-N-(4-nitrophenyl)-3-phenylpropanamide (BPNPP), 2-[N-(benzenesulfonyl)-1-phenylformamido]-3-(1H-indol-2-yl)-N-(4-nitrophenyl)propenamide (BPINP) and 2-[N-(benzenesulfonyl)-1-phenylformamido]-4-methyl-N-(4-nitrophenyl)pentanamide (BPMNP) following an environmentally friendly zinc chloride catalyst mediated synthesis. The lower value of the HOMO-LUMO energy gap (2.9756 eV) observed for BPMNP indicated its higher chemical and biological activity. The global electrophilicity index (ω), which is related to chemical hardness and chemical potential in line with other global descriptors showed that the order of reactivity is BPMNP > BPINP > BPNPP > BPNA. The NBO analysis showed that σ → σ*, σ* →π*, π → π*, and π* → π* transitions were observed in all the compounds while σ → σ* and π* → π* showed the lowest and the highest stabilization energy, respectively. From the molecular docking analysis, BPMNP again, showed the most stable binding energy of − 9.6 kcal/mol and bond length of 1.99 Å, evidently performing better than the standard drug with binding energy and bond length of −7.6 kcal/mol and 2.89 Å, respectively. The binding energy obtained was observed to follow a decreasing order as thus; BPMNP > BPINP > BPNA > BPNPP which strongly indicates alkane-substituted benzenesulphonamide carboxamides especially BPINP and BPMNP possess potent curative properties against trypanosomiasis. [ABSTRACT FROM AUTHOR]

An optimal balance between excitatory and inhibitory transmission in the central nervous system provides essential neurotransmission for good functioning of the neurons. In the neurology field, a disturbed balance can lead to neurological diseases like epilepsy, Alzheimer’s, and Autism. One of the critical agents mediating excitatory neurotransmission is α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors, which are concerned with synaptic plasticity, memory, and learning. An imbalance in neurotransmission finally results in excitotoxicity and neurological pathologies that should be corrected through specific compounds. Hence, the current study will prove to be an evaluation of new thiazole-carboxamide derivatives concerning AMPAR-modulating activity and extended medicinal potential. In the current project, five previously synthesized thiazole-carboxamide derivatives, i.e., TC-1 to TC-5, were used to interact with the AMPARs expressed in HEK293T cells, which overexpress different subunits of the AMPAR. Patch-clamp analysis was carried out while the effect of the drugs on AMPAR-mediated currents was followed with a particular emphasis on the kinetics of inhibition, desensitization, and deactivation. All tested TC compounds, at all subunits, showed potent inhibition of AMPAR-mediated currents, with TC-2 being the most powerful for all subunits. These compounds shifted the receptor kinetics efficiently, mainly enhancing the deactivation rates, and hence acted as a surrogate for their neuroprotective potentials. Additionally, recently published structure–activity relationship studies identified particular substituent groups as necessary for improving the pharmacologic profiles of these compounds. In this regard, thiazole-carboxamide derivatives, particularly those classified as TC-2, have become essential negative allosteric modulators of AMPAR function and potential therapeutics in neurological disturbances underlain by the dysregulation of excitatory neurotransmission. Given their therapeutic effectiveness and safety profiles, these in vivo studies need to be further validated, although computational modeling can be further developed for drug design and selectivity. This will open possibilities for new drug-like AMPAR negative allosteric modulators with applications at the clinical level toward neurology.

Some furan/thiophene-2-carboxamide derivatives (1–3) were prepared from acyl chlorides and heterocyclic amine derivatives with good yields, employing synthetic route and their chemical structures were confirmed using different spectroscopic methods including IR, 1H NMR, 13C NMR and elemental analysis. Three different enzyme inhibition effect tests as urease, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibiting activities, were applied to these compounds. The biological evaluation results clearly showed that the compound 1 showed approximately 9.8-fold more activity against urease enzyme than thiourea standard while the compound 3 showed approximately 4.2-fold more activity against BChE enzyme than galantamine standard. The molecular interaction for each of the target compounds with the active sites of the urease, acetylcholinesterase and butyrylcholinesterase enzymes was investigated by molecular insertion simulations and the results were confirmed the experimental findings. The results also show that compounds such as 1 and 3 carrying thiophene/furan carbocamide moieties could be used promising structures in the development of more potent pharmaceutical agents in the future. [ABSTRACT FROM AUTHOR]

5-Chloro-N-((2-oxo-3-(4-(3-oxomorpholino) phenyl) oxazolidin-5-yl) methyl) thiophene-2-carboxamide derivatives were synthesized in a simple and efficient approach using 2-(oxiran-2-ylmethyl) isoindoline-1, 3-dione, 4-(4-aminophenyl) morpholin-3-one, and 5-chlorothiophene-2-carbonyl chloride by stepwise synthesis. Three compounds 3, 4 and 7 were designed, prepared, and screened for anticancer activity against HeLa, MCF- 7, A-549 and K-562 and antibacterial activities against Gram +ve and Gram -ve strains. The carboxamide moieties proved to be capable for the development of new anticancer and anti-bacterial agents. Docking studies carried out on target receptors caspase-3 HeLa cell line and Staphylococcus aureus DNA-Gyrase also supported the anticancer and antimicrobial activity of compounds 3, 4 and 7. [ABSTRACT FROM AUTHOR]

The reaction of maleopimaric acid and its acid chloride with 3-, 6-, and 8-aminoquinolines afforded quinoline containing maleopimarimides and carboxamides in high yields, respectively. Structure of the synthesized compounds was determined by 1Н, 13С, 1H–13C HSQC, 1H–13C HMBC, COSY, NOESY, and 1Н–15N HMBC NMR spectroscopy methods. [ABSTRACT FROM AUTHOR]

A series of novel botanical active component 4-chromanone derivatives incorporating carboxamide and 1,3,4-thiadiazole thioether moieties were synthesized and evaluated for their in vitro antibacterial and activities antifungal against Xanthomonas axonopodis pv. citri (Xac), Xanthomonas oryzae pv. oryzicolaby (Xoc) and Mucor bainieri (M. bainieri), Mucor fragilis (M. fragilis), Trichoderma atroviride (T. atroviride), respectively. Antibacterial screening results suggested that the target compounds showed moderate to good antibacterial activities against Xac and Xoc, to the contrary, had lower inhibitory effects on M. fragilis, M. bainieri, and T. atroviride. Among the target compounds, compound 6-chloro-N-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-4-oxochromane-2-carboxamide (6f) had the best inhibition rates against Xac (85.15% and 72.41%, respectivelty) and Xoc (95.14% and 82.09%) at 200 and 100 μg/mL, which were superior to Bismerthiazol and Thiodiazole copper. As far as we know, it is the first report on the design, synthesis, and bioactivity evaluation of novel 4-chromanone-derived compounds incorporating carboxamide and 1,3,4-thiadiazole thioether moieties. [ABSTRACT FROM AUTHOR]

We described here a simple and metal‐free protocol to synthesize [1,2,3]triazolo[1,5‐a]quinoline 3‐carboxamides through a two‐step synthetic strategy, in which the first step uses organocatalysis (10 mol % of diethylamine or 1,8‐diazabicyclo[5.4.0]undec‐7‐ene, while the second step involves the use of inorganic base (1.2 or 0.1 equiv. of potassium hydroxide). These reactions were performed between β‐keto amides and o‐carbonyl phenylazides in dimethylsulfoxide as solvent at 70 °C for 2 h. The synthetic protocol is ample, which thirteen examples of secondary [1,2,3]triazolo[1,5‐a]quinoline 3‐carboxamides were synthesized ranging from good to excellent yields (63‐96 %), and six different tertiary [1,2,3]triazolo[1,5‐a]quinolines 3‐carboxamides were obtained ranging from moderate to good yields (48–76 %). [ABSTRACT FROM AUTHOR]

A series of 1-[2-(4-methyl-2-(methylthio)pyrimidine-5-carboxamido)phenyl]ethyl-substitutedphenyl carbamates (3a–3i) were designed and synthesized, using 4-methyl-2-(methylthio)pyrimidine-5-carboxylic acid, (2-aminophenyl)ethan-1-one, and substituted phenyl isocyanates as starting materials. Their structures were characterized by 1H NMR, 13C NMR, IR and HRMS. The in vitro fungicidal activities against Sclerotinia sclerotiorum were evaluated, and the result showed that some compounds displayed moderate antifungal activity with >60% inhibitory rates, among which 1-[2-(4-methyl-2-(methylthio)pyrimidine-5-carboxamido)phenyl] ethyl-(2- methyl phenyl)carbamate (3a) and 1-[2-(4-methyl-2-(methylthio)pyrimidine-5- carboxamido)phenyl] ethyl-(3-trifluoromethyl phenyl)carbamate (3g) held inhibitory rates of 69.5% and 70.3% at 100 mg/L, respectively. Molecular docking study showed that 3g can form two hydrogen bonds and a cation-π interaction with succinate dehydrogenase. [ABSTRACT FROM AUTHOR]

Abstract Quinolone is a privileged scaffold in medicinal chemistry and 4-Quinolone-3-Carboxamides have been reported to harbor vast therapeutic potential. However, conversion of N-1 substituted 4-Quinolone 3-Carboxylate to its corresponding carbamates is highly restrictive. This motivated us to adopt a much simpler, scalable and efficient methodology for the synthesis of highly pure N-1 substituted 4- Quinolone-3-Carboxamides with excellent yields. Our adopted methodology not only provides a robust pathway for the convenient synthesis of N-1 substituted 4- Quinolone-3-Carboxamides which can then be explored for their therapeutic potential, this may also be adaptable for the derivatization of other such less reactive carboxylate species.

A series of carbamothioyl-furan-2-carboxamide derivatives were synthesized using a one-pot strategy. Compounds were obtained in moderate to excellent yields (56–85%). Synthesized derivatives were evaluated for their anti-cancer (HepG2, Huh-7, and MCF-7 human cancer cell lines) and anti-microbial potential. Compound p-tolylcarbamothioyl)furan-2-carboxamide showed the highest anti-cancer activity at a concentration of 20 μg/mL against hepatocellular carcinoma, with a cell viability of 33.29%. All compounds showed significant anti-cancer activity against HepG2, Huh-7, and MCF-7, while indazole and 2,4-dinitrophenyl containing carboxamide derivatives were found to be less potent against all tested cell lines. Results were compared with the standard drug doxorubicin. Carboxamide derivatives possessing 2,4-dinitrophenyl showed significant inhibition against all bacterial and fungal strains with inhibition zones (I.Z) in the range of 9–17 and MICs were found to be 150.7–295 μg/mL. All carboxamide derivatives showed significant anti-fungal activity against all tested fungal strains. Gentamicin was used as the standard drug. The results showed that carbamothioyl-furan-2-carboxamide derivatives could be a potential source of anti-cancer and anti-microbial agents. [ABSTRACT FROM AUTHOR]

In the presence of tetrabutylammonium bromide (TBAB), the cycloaddition reaction of phenacylmalononitriles with dialkyl but-2-ynedioates in acetonitrile at room temperature resulted in 3,3-dicyano-5-hydroxy-5-arylcyclopent-1-ene-1,2-dicarboxylates in high yields. More importantly, the DABCO-promoted domino reaction of two molecules of each phenacylmalononitrile and dialkyl but-2-ynedioate in acetonitrile at room temperature afforded unique multifunctionalized carboxamide-bridged dicyclopentenes in moderate to good yields and with high diastereoselectivity.

Two carboxamide complexes of BeCl2 with NH functions have been prepared and structurally characterized. Bis(2‐pyrrolidone) beryllium(II) chloride and bis(N‐phenyl acetamide) beryllium(II) chloride show extensive hydrogen bond networks in the solid state, which leads to low solubility in organic solvents. Related complexes bis(phenyl acetate) beryllium(II) chloride and bis(acetophenone) beryllium(II) chloride have also been prepared and structurally characterized. These lack hydrogen bonds in the solid state and are therefore highly soluble in chlorinated solvents. [ABSTRACT FROM AUTHOR]

Carboxamide derivatives containing p‐toluenesulfonamide functionality were synthesized by the environmentally friendly method using zinc chloride catalyst. All the synthesized compounds; 2‐N‐(4‐methylbenzenesulfonyl)‐1‐phenylformamido‐N‐(4‐nitrophenyl) acetamide (MBPNA), 2‐N‐(4‐methylbenzenesulfonyl)‐1‐phenylformamido‐N‐(4‐nitrophenyl)‐3‐phenyl propanamide (MBPNPP), 3‐(1H‐indol‐2‐yl)‐2‐N‐(4‐methylbenzenesulfonyl)‐1‐phenylformamido‐N‐(4‐nitrophenyl) propanamide (HIMBPNP) and 4‐Methyl‐2‐N‐(4‐methylbenzenesulfonyl)‐1‐phenylformamido‐N‐(4‐nitrophenyl) pentanamide (MBPNP) were characterized by FT‐IR, 1H and 13C NMR studies. Density functional theory (DFT) investigations using the B3LYP/6‐311++G (d, p) functional/basis set along with molecular docking simulations were conducted to explore their electronic structure, reactivity indexes and bioactive potentials respectively. The results of the molecular anti‐plasmodal simulation showed that the compounds are very effective drug candidates especially HIMBPNP which among them contains the Indol group. The result of the present research therefore requires further attention as it provides a suitable platform for the discovery and biological assessment of new anti‐malaria drugs. [ABSTRACT FROM AUTHOR]

A new series of 2-pyrazoline derivatives starting from substituted benzodioxole chalcones were designed and synthesized. IR and 1H NMR spectral data and elemental analysis were used to characterize the structures of the synthesized compounds. The cytotoxic activities on HeLa, MCF-7 cancer cell lines and NIH-3T3 for these compounds were tested by using MTT assay. Among the synthesized compounds 2d, 2j, 3j and 3n against MCF-7 cells, and 3c against HeLa exhibited significant cytotoxic activity with IC50 between 10.08 and 27.63 μM. Compound 3f showed the most potent anticancer activity against both cancer cells with good selectivity (IC50 = 11.53 μM on HeLa with SI = 81.75 and IC50 = 11.37 μM on MCF-7 with SI = 82.90). Furthermore, in silico ADMET analyses were performed and the drug-likeness properties of the compounds were investigated.

[Display omitted] • Small molecule-based design and synthesis of carboxamide-appended pyrazole conjugates. • 5g exhibited multifaceted potential (nuclear fragmentation, upregulation of caspase 3 and 9 etc.) against MDA-MB-231 cells. • The synergistic combination of paclitaxel and 5g has demonstrated improved efficacy by several folds. • The non-toxic nature of 5g was established in zebrafish embryos. We report the design, synthesis, and validation of carboxamide-based pyrazole and isoxazole conjugates with a multifaceted activity against Breast Cancer Cell Line MDA-MB-231. The study established that amongst the series, N -(3,5-bis(trifluoromethyl)benzyl)-3-(3,4,5-trimethoxyphenyl)-1 H -pyrazole-5-carboxamide (5 g) exhibits the highest potency in inhibiting Breast Cancer Cell Line MDA-MB-231 with an IC 50 value of 15.08 ± 0.04 µM. The MDA‐MB‐231 cells, upon treatment with compound 5 g , exhibited characteristic apoptotic specific activities such as nuclear fragmentation, phosphatidylserine translocation to the outer plasma membrane, release of lactate dehydrogenase (LDH), and upregulation of caspase 3 and caspase 9 activities. Also, the modulation of pro and antiapoptotic proteins in 5 g treated MDA-MB-231 cells was revealed by membrane array analysis. More importantly, the combination of paclitaxel and compound 5 g has exhibited improved activity by several folds via their synergistic effects. [ABSTRACT FROM AUTHOR]

[Display omitted] • Twelve new substituted benzenesulphonamoyl Cys-Gly dipeptide carboxamide derivatives were synthesized. • Characterization was done via FT-IR., 1H NMR, 13C NMR and HRMS spectroscopic techniques. • Their drug likeness was evaluated via (SwissADME) soft wares. • The antimicrobial and antimalarial in silico studies was performed via AutoDock tools (version 1.5.4). • Pharmacological studies of the compound were also carried out. Twelve new sulphonamide (Cys-Gly) dipeptide carboxamide derivatives 17a–17l were designed, prepared and characterized through spectroscopic techniques and their pharmacological properties investigated. The molecular docking analyses revealed good interactions of the derivatives with the desired amino residues active pockets. In vitro antimicrobial, in vivo antimalarial, haematological and other related tests (liver and kidney) were also conducted. Compounds 17b exhibited good minimum inhibitory concentration (MIC) results (0.9–11) mg/mL for the studied organisms when compared with ciprofloxacin and fluconazole. Derivatives 17a −17l showed parasitaemia inhibition in the range (31.11–67.78) % on the fourth day after treating the animals with 40 mg/kg of the compounds. Derivative 17b also displayed the highest parasitaemia inhibition (67.78 %) comparable with the standard (Lumenfantrine) 75.27 %. The prepared derivatives showed promising pharmacological properties with regards to hematological, liver and kidney function tests. [ABSTRACT FROM AUTHOR]

Quinolone is a privileged scaffold in medicinal chemistry and 4-Quinolone-3-Carboxamides have been reported to harbor vast therapeutic potential. However, conversion of N-1 substituted 4-Quinolone 3-Carboxylate to its corresponding carbamates is highly restrictive. This motivated us to adopt a much simpler, scalable and efficient methodology for the synthesis of highly pure N-1 substituted 4- Quinolone-3-Carboxamides with excellent yields. Our adopted methodology not only provides a robust pathway for the convenient synthesis of N-1 substituted 4- Quinolone-3-Carboxamides which can then be explored for their therapeutic potential, this may also be adaptable for the derivatization of other such less reactive carboxylate species. [ABSTRACT FROM AUTHOR]

A new series of 1-(4-methoxyphenyl)-N-substituted phenyl-1H-1,2,3-triazole-4-carboxamide derivates (4A–4N) have been synthesized in excellent yields and structures were characterized by spectral techniques like 1H-NMR, 13C-NMR, LC-MS, and FT-IR. The newly synthesized derivatives were evaluated for anticancer activity against breast cancer cell lines MCF-7 and MDA-MB-231. Among them, compound 4H (IC50 = 13.11 and 23.61 μM) and compound 4M (IC50 = 11.55–31.87 μM) shows good cytotoxicity activity toward both cell line, while compounds 4B (IC50 = 9.48 μM), 4I (IC50 = 7.11 μM), and 4J (IC50 = 8.27 μM) showed promising cytotoxicity against MCF-7 cell line as compared with standard (Doxorubicin). Also explored docking study with binding mode of interactions and active site in EGFR tyrosinse (PDB ID: 2J5F) proteins and molecular docking study shows very good interaction with the tyrosine kinase active site. In addition to this targeted compounds were studied the pharmacokinetics and the compounds were follow Lipinski's rule of five as well as compounds have acceptable good drug-likeness score properties. [ABSTRACT FROM AUTHOR]

The treatment of [Ru(η6-p-cymene)Cl2]2 with N,N'-(1,2-phenylene)dipicolinamide (H2L1) afforded the double salt complex [{Ru(η6-p-cymene)2-µ-Cl}L1][Ru(η6-p-cymene)Cl3], (Ru1) in moderate yields. Separately, the reactions of ligands (H2L1), N,N'-(4,5 dimethyl-1,2-phenylene)dipicolinamide (H2L2), and N,N'-(4-methoxy-1,2-phenylene)dipicolinamide (H2L3) with the [Ru(η6-p-cymene)Cl2]2 in the presence of KPF6 afforded the respective dinuclear half-sandwich Ru(II) complexes [{(Ru(η6-p-cymene)2--µ-Cl}L1][PF6] (Ru2), [{(Ru(η6-p-cymene)2-µ-Cl}L2][PF6] (Ru3), and [{(Ru(η6-p-cymene)2-µ-Cl}L3][PF6] (Ru4). NMR and FT-IR spectroscopies, ESI-MS spectrometry, and elemental analyses were used to establish the molecular structures of the new dinuclear ruthenium(II) complexes. Single crystal X-ray crystallography was used to confirm the piano-stool geometry of the dinuclear complexes Ru1 and Ru4, as containing N^N chelated ligand and bridging chlorido ligands in each Ru(II) atom. The complexes (Ru1-Ru4) showed good catalytic activities at low catalyst concentrations of 0.005 mol% in the transfer hydrogenation of a wide range of ketone substrates. [ABSTRACT FROM AUTHOR]

The reaction of {[4-(3,4-dimethoxyphenyl)tetrahydro-2H-pyran-4-yl]methyl}amine with diethyl oxalate was used to synthesize ethyl 2-({[4-(3,4-dimethoxyphenyl)tetrahydro-2H-pyran-4-yl]methyl}amino)-2-oxoacetate, whose cyclization with phosphorus oxychloroxide under Bischler–Napieralski reaction conditions gave 1-carbethoxy-substituted dihydroisoquinoline. By treatment with methylamine the latter was converted to the corresponding N-methylcarboxamide derivative, which was reduced to obtain N-methyl-6,7-dimethoxy-2,2',3,3',5',6'-hexahydro-1H-spiro[isquinoline-4,4'-pyran]-1-carboxamide. A series of novel derivatives of 4-spirotetrahydropyran-substituted dihydro- and tetrahydroisoquinolines with various different substituents in the first and second positions of the heterocyclic ring were prepared. [ABSTRACT FROM AUTHOR]

The present study describes an efficient access to enantioenriched pyrimidines' derivatives from readily available Boc-AA-NH2 and β-enaminones. This strategy allows the synthesis of a large variety of chiral pyrimidines (18 examples) with good yields from the chiral pool. In the case of peptide isosteres, this procedure proved to be highly stereoretentive and paves the way to the construction of C-terminal modified peptidomimetics as illustrated in the synthesis of two original pyrimidines containing pseudo-dipeptides. [ABSTRACT FROM AUTHOR]

A series of N-heteroaryl substituted Gallamide derivatives 3a-3g were synthesised and the obtained structures were further confirmed by different spectral studies. For in-vitro antibacterial activity, the synthesised compounds were evaluated against three UTI (Urinary Tract Infection) bacterial strains including Staphylococcus aureus, Escherichia coli, and Streptococcus pyogenes. Furthermore, the designed compounds were docked with bacterial DNA gyrase and dihydropteroate synthase. All the compounds had shown good inhibition against S. aureus whereas compound 3e has produced significant inhibition at 28 and 26 mm against S.aureus and E.coli, respectively. The MIC value of the conjugate 3e and 3d was 3.12 and 6.25 μg/mL against S. aureus andE.coli, respectively. Compound 3,4,5-trihydroxy-N-(4-(N-(5-methyl isoxazol-3-yl) sulfamoyl) phenyl)benzamide 3d had shown the highest binding energy against both the targets along with good antibacterial action. [ABSTRACT FROM AUTHOR]

Background and purpose: The preponderance of microbial infections remains a global challenge. In the present study, synthesis of novel cysteine-based antimicrobial agents and their biological evaluation is reported. Experimental approach: The reaction of p-toluenesulphonyl chloride with cysteine afforded 2-{[(4-methylphenyl)sulphonyl]amino}-3-sulphanylpropanoic acid [3] which was acetylated based on Lumiere-Barbier method using acetic anhydride. The ammonolysis of the acetylated compound [4] gave the carboxamide derivative [5] which reacted with aniline, aminopyridine and diaminopyrimidine via nickel catalyzed Buchwald-Hartwig amidation reaction to afford compounds 6a, 6b, and 6c, respectively. The compounds were characterized using FTIR, 1H-NMR, 13C-NMR, and elemental analysis. The in vitro antimicrobial activities were determined. Their physicochemical properties were generated in silico and the molecular docking studied bacterial and fungal infections. Findings/Results: Compounds 4, 6b, and 6c exhibited excellent in vitro antibacterial activities while compound 4 had the best antifungal activities. From the in silico antimicrobial results, compound 3 had a better binding affinity (-10.95 kcal/mol) than penicillin (-10.89 kcal/mol) while compounds 3 and 4 had binding affinities (-10.07 and -10.62kcal/mol) comparable to ketoconazole (-10.85 kcal/mol). Conclusion and implication: All the synthesized compounds exhibited significant antibacterial and antifungal activities and were confirmed to be potential antimicrobial agents.

The present study was carried out to design and synthesize a number of novel aromatic carboxamide derivatives of dehydroabietylamine. The preliminary antifungal assay indicated that most of title compounds displayed moderate to good antifungal activity toward the six fungal strains in vitro. Compounds 3i, 3q, 4b and 4d showed significant antifungal activity against Sclerotinia sclerotiorum, with EC50 values ranging from 0.067 ∼ 0.393 mg/L. Compounds 3i, 4b and 4d also showed pronounced mycelial growth inhibition activities against B. cinerea and A. solani. Furthermore, in the in vivo assay, compound 4b exhibited brilliant protective activity against S. sclerotiorum-infected rape leaves. Meanwhile, the in vivo bioassay on tomato plants infected by B. cinerea showed that compound 3i and 4d displayed excellent protective activity at 200 mg/L, which were near to boscalid. Primary mechanistic study revealed that 4b could inhibit sclerotia formation as well as reduce the exopolysaccharide level. SEM and TEM analysis indicated that 4b possessed a strong ability to destroy the surface morphology of mycelia, cell structure and seriously interfere with the growth of the fungal pathogen. In addition, 4b exhibited good inhibitory activity (IC50 = 23.3 ± 1.6 μM) toward succinate dehydrogenase (SDH). Molecular modeling study confirmed the binding modes between compound 4b and SDH. The above antifungal results and fungicidal mechanism study revealed that this class of dehydroabietylamine derivatives could be potential SDH inhibitors and lead compounds for novel fungicides development.

Coumarin compounds have a variety of biological activities such as anti-tumor, anti-coagulation, anti-HIV, anti-fungal, and insecticidal. Amide and sulfonamide compounds have been used as fungicides for half a century, and dozens of varieties have been developed so far. This study focused on the introduction of carboxamide and sulfonamide moieties in a coumarin core to discover novel derivatives. Based on this strategy, we synthesized two series of novel carboxamide and sulfonamide substituted coumarin derivatives, and their fungicidal activity was also investigated. Some designed compounds possessed potential activities against six phytopathogenic fungi in the primary assays, highlighted by compound 6r. Compound 6r exhibited stronger fungicidal activity against Botrytis cinerea (EC50 = 20.52 µg/mL) and will be the lead structure for further study. [ABSTRACT FROM AUTHOR]

The apoptotic antiproliferative actions of our previously reported CB1 allosteric modulators 5-chlorobenzofuran-2-carboxamide derivatives VIIa–j prompted us to develop and synthesise a novel series of indole-2-carboxamide derivatives 5a–k, 6a–c, and 7. Different spectroscopic methods of analysis were used to validate the novel compounds. Using the MTT assay method, the novel compounds were examined for antiproliferative activity against four distinct cancer cell lines. Compounds 5a–k, 6a–c, and 7 demonstrated greater antiproliferative activity against the breast cancer cell line (MCF-7) than other tested cancer cell lines, and 5a–k (which contain the phenethyl moiety in their backbone structure) demonstrated greater potency than 6a–c and 7, indicating the importance of the phenethyl moiety for antiproliferative action. Compared to reference doxorubicin (GI50 = 1.10 µM), compounds 5d, 5e, 5h, 5i, 5j, and 5k were the most effective of the synthesised derivatives, with GI50 ranging from 0.95 µM to 1.50 µM. Compounds 5d, 5e, 5h, 5i, 5j, and 5k were tested for their inhibitory impact on EGFR and CDK2, and the results indicated that the compounds tested had strong antiproliferative activity and are effective at suppressing both CDK2 and EGFR. Moreover, the studied compounds induced apoptosis with high potency, as evidenced by their effects on apoptotic markers such as Caspases 3, 8, 9, Cytochrome C, Bax, Bcl2, and p53. [ABSTRACT FROM AUTHOR]

• Four mononuclear and dinuclear carboxamide Pd complexes isolated. • Molecular structures confirmed using single crystal X-ray analyses. • Interactions of the Pd complexes with CT-DNA) investigated. • BSA interactions studies established static quenching mechanism. • Cytotoxic effects of the complexes examined in three cancer cell lines. Reactions of ligands [ N 2, N 3-bis(pyridin-2-yl)pyrazine-2,3-dicarboxamide] (L1), [ N 2, N 3-bis(6-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide] (L2), [ N 2, N 3-bis(4-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide] (L3) and [ N 2, N 3-bis(quinoline-8-yl)pyrazine-2,3-dicarboxamide] (L4) with [PdCl 2 (NCMe) 2 ] afforded the respective palladium(II) complexes: [Pd 2 (L1) 2 Cl 2 ] (Pd1) , [Pd 2 (L2) 2 Cl 2 ] (Pd2) , [Pd 2 (L3) 2 Cl 2 ] (Pd3) and [Pd(L4) Cl] (Pd4). Molecular structures of complexes Pd1 and Pd3 are dinuclear containing two bridging bidentate ligand units. The interactions of the palladium complexes (Pd1 - Pd4) with calf thymus DNA (CT-DNA) were monitored using UV–Vis and fluorescence spectroscopy and revealed intercalative binding modes, with intrinsic binding constants (K b) in the order of 106 M−1. Bovine serum albumin (BSA) interaction was evaluated using fluorescence techniques and displayed a static quenching mechanism. The cytotoxic effects of the complexes Pd1-Pd4 were examined against human breast cancer cell lines MCF-7 and MDA-MB-231, and human transformed lung cell line MRC5-SV2 (a model of lung cancer) and its parental normal lung fibroblast cell line MRC5. While the complexes Pd1 and Pd4 showed significant to moderate cytotoxicity against MCF-7 (IC 50 of 11.2 µM and 61.5 µM, respectively), complexes Pd2 and Pd3 were inactive. All the complexes were inactive against the MDA-MB-231 cell line, and Pd2-Pd4 were inactive against the MRC5-SV2 cell line. Compounds Pd1 exhibited lower cytotoxicity against the normal cell line MRC5. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, using the botanical active components of carvacrol, thymol, guaiacol, and sesamol as the lead structures, 19 novel botanical active component derivatives containing carboxamide and 1,3,4-thiadiazole thioether moieties (5a−5s) were synthesized and structurally characterized by 1H NMR, 13C NMR, and HRMS. The antibacterial bioassay results in vitro showed that compound 2-(2-methoxyphenoxy)-N-(5-(methylthio)-1,3,4-thiadiazol-2-yl)acetamide (5k) revealed excellent inhibitory activities against Xanthomonas axonopodis pv. citri (Xac) and Xanthomonas oryzae pv. oryzicolaby (Xoc), with the median effective concentration (EC50) values of 22 and 15 μg/ml, respectively, which were even better than those of thiodiazole copper and bismerthiazol. Meanwhile, all the target compounds revealed lower in vitro inhibitory effects on Mucor bainieri (M. bainieri), Mucor fragilis (M. fragilis), and Trichoderma atroviride (T. atroviride), than carbendazim.