Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents

In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol (3, 4), 3,4-dihydroquinoline (7, 8) and thiopyran (10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9) was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities against Candida albicans and Aspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid (9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent.

Eco-Friendly Synthesis and Comparative In Vitro Biological Evaluation of Silver Nanoparticles Using Tagetes erecta Flower Extracts

The present study reports an eco-friendly synthesis method of silver nanoparticles (AgNPs) using two different extracts (aqueous and ethanolic) of Tagetes erecta flowers. When exposed to different biocompounds found in the plant, silver ions are reduced, thus, resulting in the green synthesis of nanoparticles. After performing the optimization of synthesis, the obtained AgNPs were characterized using various techniques. The UV–Vis spectrum of the synthesized nanoparticles showed maximum peaks at 410 and 420 nm. TEM analysis revealed that the particles were spherical with a size ranging from 10 to 15 nm, and EDX analysis confirmed the presence of silver metal. The average diameter value obtained through DLS analysis for the two types of AgNPs (obtained using aqueous and ethanolic extracts) was 104 and 123 nm. The Zeta potentials of the samples were −27.74 mV and −26.46 mV, respectively, which indicates the stability of the colloidal solution. The antioxidant and antimicrobial activities assays showed that nanoparticles obtained using the aqueous extract presented enhanced antioxidant activity compared to the corresponding extract, with both types of AgNPs exhibiting improved antifungal properties compared to the initial extracts.

Synthesis and Biological Evaluation of Benzo[b]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant Staphylococcus aureus

The benzo[b]thiophene nucleus and the acylhydrazone functional group were combined to prepare three new series of compounds for screening against Staphylococcus aureus. The reaction of substituted benzo[b]thiophene-2-carboxylic hydrazide and various aromatic or heteroaromatic aldehydes led to a collection of 26 final products with extensive structural diversification on the aromatic ring and on position 6 of the benzo[b]thiophene nucleus. The screening lead to the identification of eight hits, including (E)-6-chloro-N’-(pyridin-2-ylmethylene)benzo[b]thiophene-2-carbohydrazide (II.b), a non-cytotoxic derivative showing a minimal inhibitory concentration of 4 µg/mL on three S. aureus strains, among which were a reference classical strain and two clinically isolated strains resistant to methicillin and daptomycin, respectively.

Nitrophenyl-group-containing Heterocycles. Part I. Synthesis, Characterization, Anticancer Activity and Antioxidant Properties of Some New 5,6,7,8-tetrahydro-isoquinolines Bearing 3(4)-nitrophenyl Group

Regioselective cyclocondensation of 2,4-diacetyl-5-hydroxy-5-methyl-3-(3-nitrophenyl/4-nitrophenyl)cyclohexanones 1a,b with cyanothioacetamide afforded the corresponiing 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(3-nitrophenyl/4-nitrophenyl)-5,6,7,8-tetrahydro-soquinoline-3(2H)-thiones 2a,b in 93-96% yield. Reaction of compounds 2a,b with some ethyl iodide, 2-chloroacetamide (4a) or its N-aryl derivatives 4b-e by refluxing in ethanol, in the presence of slightly excess molar amounts of sodium acetate trihydrate, for one hour gave 3-ethylthio-5,6,7,8-tetrahydro-isoquinoline 3 and (5,6,7,8-tetrahydroisoquinolin-3-ylthio)acetamides 5a-i, respectively. On heating compounds 5b-d,f,g in ethanol containing a catalytic amount of sodium carbonate, they converted into their isomeric 1-amino- 6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxamides 6b-d,f,g. Structural formulae of all synthesized compounds were characterized on the basis of their elemental analyses and spectroscopic data. Also, the biological evaluation of the synthesized isoquinolines as anticancer and antioxidant agents have been carried out and the obtained results are reported herein.