Synthesis, spectral analysis and pharmacological study of N'- substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazides

A series of molecules bearing multiple functional groups were synthesized to study their antibiotic effect against Gram-positive and Gram-negative bacteria and lipoxygenase activity as well. 2,4-Dimethylcarbolic acid (1) was refluxed with ethyl 2-bromoacetate to synthesize ethyl 2-(2,4-dimethylphenoxy)acetate (2). Compound 2 was converted to the corresponding hydrazide 3, again on refluxing with hydrazine. The compound 5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-thiol (4) was synthesized by the reaction of 3 and CS2 in the presence of KOH. Compound 4 was further converted to the corresponding ester 5 and then 2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide (6). The final molecules N'-substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide, 8a-m, bearing ether, 1,3,4-oxadiazole, thioether, hydrazone and azomethine functional groups were synthesized by stirring the aryl carboxaldehydes 7a-m with 6 in methanol at room temperature. The depicted structures of all synthesized molecules were corroborated by IR, 1H-NMR and EIMS spectral data analysis. 8m and 8i showed substantial antibacterial activity and lipoxygenase inhibitory activity, respectively

Synthesis of 3-[4-(2-furoyl)-1-piperazinyl]-N- (substituted)propanamides as promising antibacterial agents with mild cytotoxicity

Purpose: To evaluate the antibacterial activity and cytotoxicity of a series of molecules with amalgamation of furoyl, piperazine and amide moieties.Methods: New derivatives, namely 3-[4-(2-furoyl)-1-piperazinyl]-N-(substituted) propanamides, were synthesized and evaluated for their antibacterial activity and toxicity to mammalian cells. The synthesis was initiated by treating different aryl/aralkyl amines (1a-u) with 3-bromopropionyl chloride (2) to obtain the solid electrophiles 3a-u, which were collected by filtration. Thereafter, the different N-aryl/aralkyl-3- bromopropionamides (3a-u) and 2-furoyl-1-piperazine (4) at equimolar ratios were allowed to react in acetonitrile and in the presence of a base, K2CO3, to form the target compounds, 5a-u. Structural elucidation was carried out using EI-MS (electron impact mass spectrometry), IR (infrared) and 1H-NMR (proton nuclear magnetic resonance). The antibacterial activity of the synthesized compounds was evaluated against various bacterial strains. Furthermore, hemolysis was determined to assess cytotoxicity using bovine red blood cells.Results: Molecules 5g, 5a, 5p, 5g and 5i were found to be potent agents against S. aureus, S. typhi, P. aeruginosa, E. coli and B. subtilis with respective minimum inhibitory concentration (MIC) values of 8.34 ± 0.55, 8.37 ± 0.12, 8.65 ± 0.57, 8.97 ± 0.12 and 9.24 ± 0.50 μM, compared to 7.80 ± 0.19, 7.45 ± 0.58, 7.14 ± 0.58, 7.16 ± 0.58 and 7.29 ± 0.90 μM for the reference standard, ciprofloxacin. The most active compounds, 5a, 5g, 5i and 5p, showed a hemolysis of 15.48, 8.03, 5.52 and 4.35 %, respectively.Conclusion: The synthesized compounds exhibit good antibacterial activity. The hemolysis data indicate that these compounds have a low toxicity level. However, in vivo studies are required to ascertain their potentials as new drug candidates.Keywords: 4-(2-Furoyl)-1-piperazine, 1H-NMR, EI-MS, Antimicrobial activity, Hemolytic activit

Synthesis of 2-{[5-(aralkyl/aryl)-1,3,4-oxadiazol-2- yl]sulfanyl}-N-(4-methyl-1,3-thiazol-2-yl)acetamides: Novel bi-heterocycles as potential therapeutic agents

Purpose: To evaluate the therapeutic potential of new bi-heterocycles  containing a 1,3-thiazole and 1,3,4-oxadiazole in the skeleton against Alzheimer's disease and diabetes, supported by in-silico study. Methods: The synthesis was initiated by the reaction of 4-methyl- 1,3-thiazol-2-amine (1) with bromoacetyl bromide (2) in aqueous basic medium to obtain an electrophile,2-bromo-N-(4-methyl-1,3- thiazol- 2-yl)acetamide (3). In parallel reactions, a series of carboxylic acids, 4a-r, were converted through a sequence of three steps, into respective 1,3,4-oxadiazole heterocyclic cores, 7a-r, to utilize as nucleophiles. Finally, the designed molecules, 8a-r, were synthesized by coupling 7a-r individually with 3 in an aprotic polar solvent. The structures of these bi-heterocycles were elucidated by infrared (IR), electron ionization-mass spectrometry (EI-MS), proton nuclear magnetic resonance (1H-NMR) and carbon nuclear magnetic resonance (13C-NMR). To evaluate their enzyme inhibitory potential, 8a-r were screened against acetylcholinesterase (AChE), but brine shrimp lethality bioassay.Results: The most active compound against AChE was 8l with half-maximal inhibitory concentration (IC50) of 17.25 ± 0.07 μM. Against BChE, the highest inhibitory effect was shown by 8k (56.23 ± 0.09 μM). Compound 8f (161.26 ± 0.23μM) was recognized as a fairly good inhibitor of urease. In view of its inhibition of α-glucosidase, 8o (57.35 ± 0.17μM) was considered a potential therapeutic agent.Conclusion: The results indicate that some of the synthesized products with low toxicity exhibit notable enzyme inhibitory activity against selected enzymes compared with the reference drug, and therefore, are of potential therapeutic interestKeywords: 4-Methyl-1,3-thiazol-2-amine,1,3,4-Oxadiazole,  Cholinesterases, α-Glucosidase, Urease, Brine shrim

S-Alkylated/aralkylated 2-(1H-indol-3-yl-methyl)-1,3,4- oxadiazole-5-thiol derivatives. 2. Anti-bacterial, enzymeinhibitory and hemolytic activities

Purpose: To evaluate the antibacterial, enzyme-inhibitory and hemolytic activities of Salkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol  derivatives.Methods: Antibacterial activities of the compounds were evaluated using broth dilution method in 96 well plates. Enzyme inhibitory activities assays were investigated against α-glucosidase, butyrylcholinesterase (BchE) and lipoxygenase (LOX) using acarbose, eserine and baicalien as reference standards, respectively. A mixture of enzyme, test compound and the substrate was incubated and variation in absorbance noted before and after incubation. In tests for hemolytic activities, the compounds were incubated with red blood cells and variations in absorbance were used as indices their hemolytic activities.Results: The compounds were potent antibacterial agents. Five of them exhibited very good antibacterial potential similar to ciprofloxacin, and had minimum inhibitory concentrations (MIC) of at least 9.00 ± 4.12 μM against S. aureus, E.coli, and B. subtilis. One of the compounds had strong enzyme inhibitory potential against α-glucosidase, with IC50 of 17.11 ± 0.02 μg/mL which was better than that of standard acarbose (IC50 38.25 ± 0.12 μg/mL). Another compound had 1.5 % hemolytic activity. Conclusion: S-Alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol deviratives with valuable antibacterial, anti-enzymatic and hemolytic activities have been successfully synthesized. These compounds may be useful in the development of pharmaceutical products.Keywords: 2-(1H-Indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol derivatives, Enzyme inhibition, Antibacterial activity, Hemolytic activity, Molecular dockin

In vitro biological assessment of 1,3,4-oxadiazole sandwiched by azinane and acetamides supported by molecular docking and BSA binding studies

The 1,3,4-Oxadiazole is an aromatic heterocyclic moiety recognized in drug research for its low lipophilicity. The multiple functionalities, heterocyclic azinane, sulfonamide, 1,3,4-oxadiazole and acetamide, are combined collectively to enhance the bioactivity potential of synthesized molecules. All the compounds were acquired by following microwave assisted and conventional techniques in a comparative way. The synthesized derivatives were screened for their antibacterial and enzyme inhibition potential. Furthermore, BSA binding analysis was executed to infer about the interaction with serum albumin. The spectral data of IR, EI-MS, 1H-NMR and 13C-NMR were used to elucidate the final structures of compounds. The synthesized compounds had a modest antibacterial potential. Compound 8f bearing 2-methyl-4,5-dinitrophenyl group was the most active one against all the bacterial strains taken into account and α-glucosidase enzyme. Compound 8d bearing 4-nitrophenyl group was the best acetyl cholinesterase inhibitor and 8i bearing phenylethyl group was the best urease inhibitor

Synthesis, characterization and pharmacological evaluation of different 1,3,4-oxadiazole and acetamide derivatives of ethyl nipecotate

A new series of N-substituted derivatives of 2-[(5-{1-[(4-chlorophenyl)sulfonyl]-3-piperidinyl}-1,3,4-oxadiazol-2-yl)sulfanyl]acetamide (6a-w) has been designed and synthesized with multifunctional moieties. The synthesized compounds were evaluated for their antibacterial and anti-enzymatic potential supported by % hemolytic activity. The synthesized compound 5-(1-(4-chlorophenylsulfonyl)-3-piperidinyl)-1,3,4-oxadiazole-2-thiol (3) was stirred with synthesized electrophiles as N-aryl/alkyl/aralkyl-2-bromoacetamide (5a-w) in an aprotic solvent under basic conditions to acquire the target molecules, 6a-w. The spectral analytical techniques of IR, EI-MS, 1H NMR and 13C-NMR were utilized for structural elucidation of synthesized molecules. The antibacterial screening against certain bacterial strains of gram-negative and gram-positive bacteria rendered compound 6i as good inhibitor of gram-negative bacterial strains. The enzyme inhibition revealed low potential against lipoxygenase (LOX) enzyme. The hemolytic study provided valuable information about cytotoxic behavior of synthesized molecules. Keywords: 1,3,4-Oxadiazole, Acetamide, Antibacterial activity, Hemolytic activity, Lipoxygenase inhibitio

Synthesis, spectral analysis and pharmacological study of N'- substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazides

ABSTRACT A series of molecules bearing multiple functional groups were synthesized to study their antibiotic effect against Gram-positive and Gram-negative bacteria and lipoxygenase activity as well. 2,4-Dimethylcarbolic acid (1) was refluxed with ethyl 2-bromoacetate to synthesize ethyl 2-(2,4-dimethylphenoxy)acetate (2). Compound 2 was converted to the corresponding hydrazide 3, again on refluxing with hydrazine. The compound 5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-thiol (4) was synthesized by the reaction of 3 and CS2 in the presence of KOH. Compound 4 was further converted to the corresponding ester 5 and then 2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide (6). The final molecules N'-substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide, 8a-m, bearing ether, 1,3,4-oxadiazole, thioether, hydrazone and azomethine functional groups were synthesized by stirring the aryl carboxaldehydes 7a-m with 6 in methanol at room temperature. The depicted structures of all synthesized molecules were corroborated by IR, 1H-NMR and EIMS spectral data analysis. 8m and 8i showed substantial antibacterial activity and lipoxygenase inhibitory activity, respectively

In vitro assessment of the protection from oxidative stress by various fractions of Artemisia incisa Pamp.

The methanolic extract of Artemisia incisa Pamp. was dissolved in distilled water and successively partitioned with n-hexane, chloroform, ethyl acetate and n-butanol. The antioxidant potential of all these fractions and remaining aqueous fraction was evaluated by four methods, i.e., the scavenging activity of the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), the total antioxidant activity, the ferric reducing antioxidant power (FRAP) assay and the ferric thiocyanate assay. In addition, the total phenolics was determined. The obtained results revealed that among the studied fractions the ethyl acetate soluble fraction showed the most potent DPPH-radical scavenging activity with an IC50 value of 5.3 ± 0.71 μg mL-1, which is even more effective than the standard antioxidant butylated hydroxytoluene (BHT) (IC50 value 0f 12.1± 0.92 μg mL-1). The ethyl acetate fraction also showed the highest FRAP value (3677.13 ± 27.1 μg TE mL-1), inhibition of lipid peroxidation (60.93 ± 0.84 % at 500 μg mL-1) and total phenolic content (95.5 ± 0.05 μg GAE g-1) as compared to other fractions. However, the remaining aqueous fraction was found to posses the highest antioxidant activity of all the fractions