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Abstract: Regarding the critical role of amyloid-β plaques in the pathogenesis of Alzheimer's disease, a series of aminoimidazo[1,2-a]pyridine derivatives were designed and synthesized as potential anti-BACE1 agents targeting the production of amyloid-β plaques. In vitro biological results demonstrated that compounds 7b and 7f exhibited the best inhibitory potency against BACE1 with IC50 values of 22.48 ± 2.06 and 30.61 ± 3.48 μM, respectively. Also, the ligand-protein docking evaluations revealed that compounds 7b and 7f could effectively bind with the different pockets of BACE1 through different interactions with the residue of the active site. The results of current studies underline the potential role of aminoimidazo[1,2-a] pyridine-containing pyrazole derivatives for developing novel BACE1 inhibitors.

The exposure of lead in workplace air and human workers of battery manufacturing factory was evaluated determined by nanotechnology since 2019-2020. Human whole blood (HWB) for subject and healthy peoples (25-55, Men, 40 N) and workplace air (40N) was prepared based on NIOSH sampling. 10 mL of HWB samples added to 20 mg of mixture ionic liquid/ ligand ([HMIM][PF6]/APDC) modified on graphene oxide nanostructures(GONs) at pH=6. After sonication, the lead ions separated/extracted by dispersive ionic liquid solid phase micro extraction (DIL-SPME) and determined by flame atomic absorption spectrometry (F-AAS). All air samples in workplace were analyzed based on NIOSH process. The results showed us the negative correlation between Pb concentration in human blood subject and healthy peoples (r=0.24). The range concentrations of lead in human subject, healthy peoples and workplace air were obtained 193.4-543.7 µg L-1, 85.6-175.9 µgL-1 and 44.7-81.5 µgm-3, respectively. The LOD, linear rang, enrichment factor(EF) and RSD% were achieved 1.25 µg L-1, 5.0- 310 µg L-1, 19.6 and less than 5% by procedure. The method was validated by standard reference material (SRM), the electrothermal atomic absorption spectrometry (ET-AAS) and ICP-MS analyzer for human samples.

In this work, new indole-acrylamide-1,2,3-triazole derivatives 9a–j were synthesized via simple and efficient chemical reactions and screened for in vitro anti-α-glucosidase activities. All the synthesized derivatives exhibited excellent α-glucosidase inhibition in the range of IC50 = 65.0 ± 0.8 − 396.3 ± 0.7 µM as compared to the standard inhibitor acarbose (IC50 = 750.0 ± 1.5 µM). Furthermore, kinetic, docking, and toxicity evaluation of the title compounds were also performed.

A novel series of (thio)barbituric-phenoxy-N-phenylacetamide derivatives 7a-l was synthesized and evaluated against Helicobacter pylori urease. The latter assay revealed that all the synthesized compounds 7a-l (IC50 = 0.69 ± 0.33–2.47 ± 0.23 μM) were significantly more potent than two used standard inhibitors, thiourea (IC50 = 23 ± 0.73 μM) and hydroxyurea (IC50 = 100 ± 1.7 μM). Docking study of the synthesized compounds demonstrated that these compounds as well fitted in the urease active site. Moreover, molecular dynamic study of the most potent compound 7d showed that this compound created important interactions with the active site flap residues, Cys592 and His593. Furthermore, in silico pharmacokinetic study predicted that all the synthesized compounds are drug-like.

A new series of phthalimide-benzamide-1,2,3-triazole hybrids 8a–k as α-glucosidase inhibitors was designed and synthesized. The biological evaluation of compounds 8a–k against yeast α-glucosidase demonstrated that all they have excellent inhibitory activity in comparison with standard inhibitor acarbose. Among them, the most potent compound was compound 8d with inhibitory activity 18.5-fold more than acarbose. Kinetic study revealed that α-glucosidase inhibition of compound 8d was the competitive type. Furthermore, docking study suggested that compound 8d is more stable than acarbose in the active site of α-glucosidase.

Regarding the critical role of amyloid-β plaques in the pathogenesis of Alzheimer's disease, a series of aminoimidazo[1,2-a]pyridine derivatives were designed and synthesized as potential anti-BACE1 agents targeting the production of amyloid-β plaques. In vitro biological results demonstrated that compounds 7b and 7f exhibited the best inhibitory potency against BACE1 with IC

In this study, a series of novel compounds based on 5-(5-nitrothiophene-2-yl)-1,3,4-thiadiazole possessing (het) aryl thio pendant at C-2 position of thiadiazole ring is developed and evaluated as antileishmanial agents using MTT colorimetric assay. 10 New compounds containing aryl and heteroaryl derivatives, started from thiophene-2-carbaldehyde in five steps, were synthesized in good to excellent yields and characterized by 1H-NMR, 13C-NMR, and IR spectroscopy. Through the compounds 6a-j, methylimidazole containing derivative 6e was recognized as the most active compound against L. major promastigotes exhibiting IC50 values of 11.2µg/mL and 7.1µg/mL after 24 and 48 h, respectively. This compound is > 4 fold more effective than Glucantime as a standard drug (IC50 = 50 µg/mL after 24 h and 25 µg/mL after 48 h).

Chromenoquinolines have been prepared via an efficient one-pot, multi-component reaction of 4-hydroxy coumarin, aqueous ammonia, dimedone and different aldehydes.

A series of substituted phenylcarbamoyl methyl benzylcarbamodithioates have been synthesized using the multicomponent condition. The reaction proceeded under mild practical condition and afforded the desired products in good yields.

A series of dihydrochromeno[4,3-b]pyrazolo[4,3-e]pyridines has been synthesized using a simple and efficient one-pot, three-component procedure. The products were obtained in good yields in the presence of heterogeneous nanoporous acid catalyst (SBA-Pr-SO3H).

A series of chromene-fused coumarins known as 10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-diones 4a–o were synthesized through one-pot reaction of appropriate benzaldehydes, dimedone, and 4-hydroxycoumarin in the presence of nano-silica sulfuric acid under solvent-free condition in good yields. The in vitro anticholinesterase assay revealed that the 3-hydroxyphenyl analog 4e showed the highest inhibitory activity against both acetylcholinesterase and butyrylcholinesterase, possessing IC50 values of 3.28 and 2.19 µM, respectively. The structure-activity relationships study demonstrated that the selectivity for acetylcholinesterase over butyrylcholinesterase could be modulated by introducing second hydroxyl or methoxy substituent on the para-position of the 3-hydroxyphenyl pendent group. The docking study of compound 4e with acetylcholinesterase confirmed π–π stacking interaction between the coumarin moiety and Trp279 as well as the formation of hydrogen bonding between hydroxyl group and Asn85.

A Series of Novel Ninhydrin-derived Spiro-quinazolinone Derivatives in Moderate to Good Yields Have Been Synthesised Through a Ferric Chloride Catalysed Reaction in 1,2-dichloroethane.

Cu(II)-β-cyclodextrin-catalyzed synthesis of spiro[indoline-3,4′-pyrano[3,2-c]chromene]-3′-carbonitriles through the reaction of isatin derivatives, 4-hydroxycoumarin, and malononitrile in ethanol at room temperature.

The title compounds are prepared by reaction of ninhydrin with aminobenzamides in moderate to good yields using ferric chloride as catalyst.

A novel series of potential phosphodiesterase-4 (PDE-4) inhibitors, 6-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, were developed. Different concentrations of the synthesized compounds were tested on cultured NIH-3T3 cells to determine their safety and efficacy in NIH-3T3 mouse fibroblastic cells in comparison with rolipram, a selective PDE-4 inhibitor. The viability of cells was determined by (3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazoliumbromide (MTT) assay. The PDE inhibition rate was measured indirectly by determination of concentrations of extracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) using enzyme-linked immunoassay technique. The results showed that all tested compounds caused a marked increase in the concentration of cAMP, whereas the concentration of cGMP stayed approximately unchanged. The cytotoxic IC(50) of all synthesized compounds was approximately twofold greater than their required concentration for inhibition of PDE-4 (in terms of elevation of cAMP), and thus, these structures could be used to develop potent and safe inhibitors of PDE-4 enzyme.

An intramolecular bromonium ion–assisted cyclization with sulfur as an internal nucleophile is described. Starting from benzoyl chlorides, this method provides an easy procedure for the synthesis of dihydrothiazole derivatives in moderate to good yields.

An intramolecular bromonium ion-assisted cyclization with sulfur as an internal nucleophile is described. Starting from benzoyl chlorides, this method provides an easy procedure for the synthesis of dihydrothiazole derivatives in moderate to good yields.

An intramolecular bromonium ion–assisted cyclization with sulfur as an internal nucleophile is described. Starting from benzoyl chlorides, this method provides an easy procedure for the synthesis of dihydrothiazole derivatives in moderate to good yields.

Nitro-containing heteroaromatic derivatives structurally related to nitroimidazole (Metronidazole) are being extensively evaluated against Helicobacter pylori isolates. On the other hand, 1,3,4-thiadiazole derivatives have also demonstrated promising antibacterial potential. In present study, we evaluated anti-H. pylori activity of novel hybrid molecules bearing nitroaryl and 1,3,4-thiadiazole moieties. Anti-H. pylori activity of novel 5-(5-nitroaryl)-1,3,4-thiadiazole derivatives bearing different bulky alkylthio side chains at C-2 position of thiadiazole ring, were assessed against three different metronidazole resistant H. pylori isolates by paper disk diffusion method. Most of the compounds demonstrated moderate to strong inhibitory response especially at 25 μg/disk. The structure-activity relationship study of the compounds demonstrated that introduction of different alkylthio moieties at C-2 position of thiadiazole ring; alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring. The promising compound of this scaffold, bearing 1-methyl-5-nitroimidazole moiety at C-5 and α-methylbenzylthio side chain at C-2 position of thiadiazole ring, showed strong inhibitory response against metronidazole resistant H. pylori isolates at 12.5 μg/disk (the inhibition zone diameter at all evaluated concentrations (12.5- 100 μg/disk) is >50 mm). Novel 5-(5-nitroaryl)-1,3,4-thiadiazole scaffold bearing different C-2 attached thio-pendant moieties with promising anti-H. pylori potential were identified. Among different nitroheterocycles, 5-nitrofuran and 5-nitroimidazole moieties were preferable for the substitution at C-5 position of 1,3,4-thiadiazole ring. Introduction of different alkylthio side chains at C-2 position of central ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring.

A novel series of potential phosphodiesterase-4 (PDE-4) inhibitors, 6-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, were developed. Different concentrations of the synthesized compounds were tested on cultured NIH-3T3 cells to determine their safety and efficacy in NIH-3T3 mouse fibroblastic cells in comparison with rolipram, a selective PDE-4 inhibitor. The viability of cells was determined by (3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazoliumbromide (MTT) assay. The PDE inhibition rate was measured indirectly by determination of concentrations of extracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) using enzyme-linked immunoassay technique. The results showed that all tested compounds caused a marked increase in the concentration of cAMP, whereas the concentration of cGMP stayed approximately unchanged. The cytotoxic IC(50) of all synthesized compounds was approximately twofold greater than their required concentration for inhibition of PDE-4 (in terms of elevation of cAMP), and thus, these structures could be used to develop potent and safe inhibitors of PDE-4 enzyme.

A series of novel 2-substituted-thio-1,3,4-thiadiazoles bearing a 5-nitroaryl moiety including nitrofuran, nitrothiophene or nitroimidazole at the 5-position and a bulky residue attached to the 2-position of the thiadiazole ring were synthesised as potential antileishmanial agents. The target compounds were evaluated against the promastigote form of Leishmania major using the tetrazolium bromide salt (MTT) colorimetric assay. All test compounds exhibited high activity against L. major promastigotes with 50% inhibitory concentrations (IC(50)) ranging from 1.11 to 3.16 μM. The structure-activity relationship study indicated that the S-pendant group attached to the 2-position of the thiadiazole ring has a high flexibility for structural alteration therefore retaining good antileishmanial activity.

A series of 5-nitroimidazole-based 1,3,4-thiadiazoles were prepared and tested for antibacterial activity against Helicobacter pylori. The anti-H. pylori activity of target compounds along with the commercially available antimicrobial metronidazole was evaluated by comparing the inhibition-zone diameters determined by the paper disc diffusion bioassay. From our bioassay results against 20 clinical isolates it is evident that piperazinyl, 4-methylpiperazinyl, 3-methylpiperazinyl, and 3,5-dimethylpiperazinyl analogs (6a, 6b, 6e, and 6f, respectively) and pyrrolidine derivative 7 had strong activity at 0.5 µg/disc (average of inhibition zone > 20 mm) while metronidazole had no activity at this dose. Compound 6f containing the 3,5-dimethylpiperazinyl moiety at the 2-position of the 5-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazole skeleton was the most potent compound tested at low concentrations.