The synthesis and evaluation of anti-acetylcholinesterase activity of some 4(3H)-quinazolinone derivatives bearing substituted 1,3,4- thiadiazole

In the present study, a series of 4(3H)-quinazolinone derivatives (5a-f) were synthesized through the cylization reaction of substituted 1,3,4-thiadiazoles containing an aromatic primary amin and anthranilic acid in the presence of acetic anhydride and acetic acid. The structures of the synthesized compounds were confirmed by elemental analysis, IR, 1 H-NMR and mass spectroscopic (5b and 5f) methods. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) using a modification of Ellman’s spectrophotometric method. Compounds 2-methyl-3-{4-[5-(ethylamino)-1,3,4-thiadiazol- 2-yl]phenyl}quinazolin-4(3H)-one (5b) and 2-methyl-3-{4-[5- (cyclohexylamino)-1,3,4-thiadiazol-2-yl]phenyl}quinazolin- 4(3H)-one (5d) can be identified as promising anticholinesterase agents due to their inhibitory effect when compared with donepezil as a reference drug

Synthesis and biological evaluation of some 1,2-disubstituted benzimidazole derivatives as new potential anticancer agents

The synthesis of some new 1-(2-aryl-2-oxoethyl)-2-[(morpholine-4-yl)thioxomethyl]benzimidazole derivatives and investigation of their anticancer activities were the aims of this work. 2-(Chloromethyl)benzimidazole compound was reacted with sulfur and morpholine via WillgerodtKindler reaction to give 2-[(morpholine-4-yl)thioxomethyl]benzimidazole. Then, the obtained compound was reacted with appropriate -bromoacetophenone derivatives in the presence of potassium carbonate to give the final products. Structure elucidation of the final compounds was achieved by FT-IR, 1H NMR spectroscopy and MS spectrometry. The anticancer activities of the final compounds were evaluated by MTT assay, BrdU method, and flow cytometric analysis on C6, MCF-7, and A549 tumor cells. Most of the synthesized compounds exhibited considerable selectivity against the MCF-7 and C6 cell lines

Synthesis of 2-(5-(2-((5-(Cyclohexylamino)-1,3,4-Thiadiazol-2-yl)thio)ethyl)-1,3,4-Oxadiazol-2-yl) Derivatives and Their Antimicrobial Activity

The rate of invasive fungal infections has increased since the 1980s, particularly in the vast populace of immunocompromised patients as well as those hospitalized with serious underlying disease [1]. [...

Synthesis and Biological Evaluation of Novel Piperazine Containing Hydrazone Derivatives

Some hydrazone derivatives were synthesized and their potential anticholinesterase activities were examined. A series of eleven new compounds of N′-(2,4-disubstitutedbenzylidene)-2-(4-(4-nitrophenyl)piperazin-1-yl)acetohydrazide derivatives were obtained via reaction of 2-[4-(4-nitrophenyl)piperazin-1-yl]acetohydrazide with aromatic aldehydes. The chemical structures of the compounds were enlightened by FT-IR, 1H-NMR, 13C-NMR, and HRMS (ESI) spectral data. The inhibition potency of the compounds 3a–k against AChE and BuChE was measured and evaluated using a modification of Ellman’s spectrophotometric method. Among the tested compounds, compound 3c was assigned to be the most active derivative. Galantamine was used as a standard drug

Synthesis and In Vitro Evaluation of New Thiosemicarbazone Derivatives as Potential Antimicrobial Agents

In an effort to develop potent antimicrobial agents, new thiosemicarbazone derivatives were synthesized via the reaction of 4-[4-(trifluoromethyl)phenyl]thiosemicarbazide with aromatic aldehydes. The compounds were evaluated for their inhibitory effects on pathogenic bacteria and yeasts using the CLSI broth microdilution method. Microplate Alamar Blue Assay was also carried out to determine the antimycobacterial activities of the compounds against Mycobacterium tuberculosis H37Rv. Among these derivatives, compounds 5 and 11 were more effective against Enterococcus faecalis (ATCC 29212) than chloramphenicol, whereas compounds 1, 2, and 12 and chloramphenicol showed the same level of antibacterial activity against E. faecalis. Moreover, compound 2 and chloramphenicol exhibited the same level of antibacterial activity against Staphylococcus aureus. On the other hand, the most potent anticandidal derivatives were found as compounds 2 and 5. These derivatives and ketoconazole exhibited the same level of antifungal activity against Candida glabrata. According to the Microplate Alamar Blue Assay, the tested compounds showed weak to moderate antitubercular activity

Synthesis and Anticandidal Activity of New Imidazole Derivatives

During the last few years, there has been an increased awareness of morbidity and mortality related to invasive and systemic fungal disease because of resistant fungi and immunocompromised infections, for instance, AIDS. [...

Design, Synthesis, and Molecular Modeling Studies of a Novel Benzimidazole as an Aromatase Inhibitor

[Image: see text] In this study, a series of novel 1,3,4-oxadiazole-benzimidazole derivatives were designed and synthesized. Their cytotoxic activities against five cancer cell lines, including A549, MCF-7, C6, HepG2, and HeLa, were evaluated by the MTT assay. The compounds 5b,c showed satisfactory potencies with much higher anticancer activity in comparison to the reference drug doxorubicin against the studied cancer cell lines. In vitro, enzymatic inhibition assays of aromatase (ARO) enzymes were performed. Molecular docking, molecular dynamics simulations, and binding free energy analyses were used to better understand the structure–activity connections and mechanism of action of the aromatase inhibitors. Two types of satisfactory 3D-QSAR (CoMFA and CoMSIA) models were generated, to predict the inhibitory activities of the novel inhibitors. Molecular docking studies were also carried out to find their binding sites and types of their interactions with the aromatase enzyme. Additionally, molecular dynamics simulations were performed to explore the most likely binding modes of compounds 5b,c with CYP19A1

Synthesis and anticandidal evaluation of new benzothiazole derivatives with hydrazone moiety

<p>In this study, we have performed the synthesis of new <i>N</i>′-(arylidene)-4-[(benzothiazol-2-yl)thio]butanoylhydrazide derivatives (<b>3a</b>–<b>s</b>) bearing azole moiety and hydrazone group in a lipophilic structural framework. The target compounds were prepared by a three step synthetic procedure starting from 2-mercaptobenzothiazole. The structures of the target compounds were elucidated by IR, ¹H NMR, ¹³C NMR spectra and elemental analysis. The antifungal activity of the obtained compounds has been determined against a number of clinic and fluconazole-resistant <i>Candida</i> strains by using microdilution method. Compounds (<b>3a</b>–<b>3s</b>) exhibited anticandidal activity in different ratios varying between the range of MIC: 50 and 200 µg/mL.</p

Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents

New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl)-1-([1,1′-biphenyl]-4-ylmethylene)thiosemicarbazide (5) was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells. Compound 5 increased early and late apoptosis in A549 and C6 cells. Compound 5 also caused disturbance on mitochondrial membrane potential and showed DNA synthesis inhibitory activity in A549 and C6 cells. Compound 5 was investigated for SIRT1 inhibitory activity to provide mechanistic insight and for that purpose docking studies were also performed for this compound on SIRT1. On the other hand, compound 5 did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between anticancer activity of compound 5 and cholinesterases