Synthesis,anticancer and antimicrobial evaluation of new pyridyl and thiazolyl clubbed hydrazone scaffolds

Abstract

A series of new hydrazones bearing pyridyl and thiazolyl scaffolds have been synthesized and evaluated for their in vitro anticancer and antimicrobial activities. The anticancer activity was evaluated against the A549 lung cancer cell line. The eight hydrazone derivatives have shown better anticancer activity than positive control doxorubicin against the A549 lung cancer cell line. The antimicrobial activity was evaluated against bacterial and fungal pathogens by using well diffusion method. The four hydrazone derivatives have displayed good antimicrobial activities. Molecular docking studies of the synthesized hydrazone derivatives revealed good binding via hydrogen bond interactions with key residues on active sites as well as neighboring residues with an active site of Focal adhesion kinase (PDB ID 2JKO). A computational study for the prediction of absorption, distribution, metabolism, and excretion (ADME) properties of all compounds has also been performed.     

Synthesis,antimicrobial activity and molecular docking of di‐ and triorganotin (IV) complexes with thiosemicarbazide derivatives

Six organotin (IV) complexes with two ligands derived from 2,3‐butanedione and thiosemicarbazide have been synthesized and fully characterized by several spectroscopic techniques, including ¹¹⁹Sn NMR and single crystal X‐ray diffraction. Reactions of the ligand diacetyl‐2‐(thiosemicarbazone)‐3‐(3‐hydroxy‐2‐naphthohydrazone), L¹H₂, with SnR₂Cl₂ (R = Me, Bu, Ph) lead to the obtaining of complexes 1 – 3 with general formula [SnR₂L¹] (R = Me 1 , R = Bu 2 , R = Ph 3 ), in which the ligand is doubly deprotonated and behaves as a N₂SO donor, whereas from the reactions of diacetyl‐2‐thiosemicarbazone, HATs, with the same organotin precursors any complex could be isolated. By contrast, reaction of HATs with SnR₃Cl induces the ligand cyclization to form a 1,2,4‐triazine‐3‐thione that binds to the metal as a monoanionic donor in a mono or bidentate manner to form compounds 4 – 6 with formula [SnR₃L²] (R = Me 4 , R = Bu 5 , R = Ph 6 ). The antimicrobial activity of the ligands and the six complexes was tested towards bacteria and fungi, including clinical isolated strains. The results show that the ligands are devoid of activity, except HATs that displays activity against Bacillus subtilis. Conversely, the complexes exhibit good antimicrobial properties against Gram positive and negative bacteria, yeasts and moulds. The best results are obtained for complexes [SnBu₃L²] 5 and [SnPh₃L²] 6 , indicating that their more lipophilic nature could play an important role in the ease of microbial cell penetration. In some cases, these complexes display similar or higher activity than that of ampicillin and miconazole, used as antibacterial and antifungal positive controls, respectively. Docking study with DHPS protein (S. aureus) has shown that out of six drugs, the compound 6 has the best binding affinity (?8.5 Kcal/mol).     

Theoretical,antimicrobial, antioxidant,in vitro cytotoxicity,and cyclin-dependent kinase 2 inhibitor studies of metal(II) complexes with bis(imidazol-1-yl)methane-based heteroscorpionate ligands

Abstract

A series of C-centered heteroscorpionate-based homoleptic manganese(II), nickel(II), and copper(II) complexes of type [M(L^1–3)₂] (1–9) have been synthesized by using the ligands (2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL¹), (4-diethylamino-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL²) and (5-bromo-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL³). The geometric parameters of the complexes were determined using UV-vis and theoretical studies suggesting distorted octahedral geometry around metal(II) ion. Frontier molecular orbital analysis supports bioefficacy of the complexes. Antimicrobial activity of the metal(II) complexes were determined against two Gram(–ve) (Escherichia coli and Klebsiella pneumoniae) and two Gram(+ve) (Bacillus cereus and Staphylococcus aureus) bacteria, and three fungal (Candida albicans, Candida glabrata, and Candida krusei) strains. Antioxidant activity of nickel(II) and copper(II) complexes were evaluated against ABTS, DPPH, and H₂O₂ free radicals. In vitro cytotoxicity activity of nickel(II) and copper(II) complexes against human breast adenocarcinoma (MCF-7), cervical (HeLa), and lung (A549) cancer cell lines along with one normal human dermal fibroblasts (NHDF) cell line were carried out by MTT assay, which shows the potent activity of copper(II) complex 8 with respect to the standard drug cisplatin. Molecular docking studies evidence the interaction of complexes with cyclin-dependent kinase 2 receptor (CDK2).     

Synthesis and evaluation of pyrazole‐incorporated monocarbonyl curcumin analogues as antiproliferative and antioxidant agents

A series of pyrazole‐incorporated monocarbonyl analogues of curcumin were synthesized via Clasien–Schimidt‐type condensation and subsequently screened for in vitro antiproliferative and antioxidant activity. The analogues 4c, 5d, 5e, 5g, 6e, and 6f showed potential activity against the MDA‐MB‐231 cell line. The synthesized analogues were also screened for their antioxidant activity. Compounds 5a , 5e , 6d, and 6f exhibit comparable radical scavenging activity with respect to the standard drug ascorbic acid. Furthermore, a molecular docking study has been conducted for 5d and 5g and suggests that these compounds have a potential to become lead molecules in drug discovery and process.     

Chemical composition,antimicrobial and antioxidant activities of the essential oil of Psammogetoncanescens

This study reports the chemical composition, antimicrobial activity and antioxidant properties of Psammogeton canescens essential oil (EO) and its main compounds. The EO was obtained from the aerial parts of P. canescens by hydrodistillation and analysed by using GC/MS. The main constituent was β-bisabolene (25%), followed by α-pinene (20%), apiole (15.34%), γ-terpinene (7.34%), p-cymene (5.35%), β-pinene (5.41%), camphene (5.12%), dill apiole (5%), myrcene (4.54%), colchicine (0.56), sylvestrene (0.56%), β-caryophyllene (0.45%), caryophyllene oxide (0.43%), (Z)-β-farnesene (0.32%), cembrene (0.21%), folic acid (0.21%), germacrene D (0.14) and β-sesquiphellandrene (0.13). β-Bisabolene exhibited strong antioxidant activity (14 ± 0.8 μg/mL). The EO of P. canescens was particularly active against Candida albicans and Escherichia coli, with the lowest minimum inhibitory concentration and minimum bactericidal/fungicidal concentration values. In conclusion, these results support the use of the EO and its main compounds for their antioxidant properties and antimicrobial activity.     

DNA interaction,antimicrobial and molecular docking studies of biologically interesting Schiff base complexes incorporating 4‐formyl‐N,N‐dimethylaniline and propylenediamine

Four new transition metal complexes incorporating a Schiff base ligand derived from propylenediamine and 4‐formyl‐N ,N ‐dimethylaniline have been synthesized using transition metal salts. The characterization of the newly formed complexes was done from physicochemical parameters and using various techniques like ¹H NMR, ¹³C NMR, IR, UV, electron paramagnetic resonance and mass spectroscopies, powder X‐ray diffraction and magnetic susceptibility. All the complexes were found to be monomeric in nature with square planar geometry. X‐ray powder diffraction illustrates that the complexes have a crystalline nature. The interaction of metal complexes with calf thymus DNA was investigated using UV–visible absorption, viscosity measurements, cyclic voltammetry, emission spectroscopy and docking analysis. The results indicate that the Cu(II), Co(II), Ni(II) and Zn(II) complexes interact with DNA by intercalative binding mode with optimum intrinsic binding constants of 4.3 × 10⁴, 3.9 × 10⁴, 4.7 × 10⁴ and 3.7 × 10⁴ M⁻¹, respectively. These DNA binding results were rationalized using molecular docking in which the docked structures indicate that the metal complexes fit well into the A‐T rich region of target DNA through intercalation. The metal complexes exhibit an effective cleavage with pUC19 DNA by an oxidative cleavage mechanism. The synthesized ligand and the complexes were tested for their in vitro antimicrobial activity. The complexes show enhanced antifungal and antibacterial activities compared to the free ligand.     

Synthesis of new annulated pyridazine derivatives and studying their antioxidant and antimicrobial activities

Benzil was reacted with cyanoacetohydrazide under microwave irradiation to give 3-oxo-5,6-diphenyl-2,3-dihydropyridazine-4-carbonitrile 1 which used as starting material for the synthesis of new heterocyclic compounds. Chlorination of pyridazinone 1 with POCl₃ afforded the chloro-pyridazine derivative 3, which then condensed with 2-aminothiazole or hydrazine hydrate to produce 3,4-diphenyl-5H-thiazolo[3′,2′:1,2]pyrimido[4,5-c]pyridazin-5-one 5 or 3-hydrazinyl-5,6-diphenylpyridazine-4-carbonitrile 6, respectively. New Schiff bases were obtained by condensation reactions of compound 6 with different aldehydes. On the other hand, compound 6 reacted with different carbon electrophiles naming acetyl acetone, diethyl malonate, and phenyl isothiocyanate producing new pyarazolo-pyridazine derivatives 11, 12, and 14, respectively. Chemical structures of all newly synthesized compounds were confirmed on the basis of spectral data and had been screened for antimicrobial and antioxidant activity.     

Synthesis,antioxidant, and anticholinesterase activities of novel N-arylsulfonyl hydrazones bearing sulfonate ester scaffold

In this research, two new series of N-arylsulfonyl hydrazone compounds ( 14 – 25 ) possessing a sulfonate moiety were synthesized and characterized by elemental analysis and various spectroscopic techniques including fourier transform infrared (FT-IR), ¹H-, and ¹³C nuclear magnetic resonance (NMR). These compounds synthesized as target molecules ( 14 – 25 ) were tested for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities and antioxidant potential. The antioxidant capacities of the tested molecules were determined by four different assays. The IC₅₀ values of the screened molecules were determined in the range of 60.14 ± 0.25–84.81 ± 1.09 μM against AChE and in the range of 70.11 ± 0.67–93.60 ± 0.47 μM against BChE. In the AChE assay, 4-hydroxybenzaldehyde-based compound 25 (60.14 ± 0.25 μM) showed the highest activity in comparison to rivastigmine (501 ± 3.08 μM). This compound (71.42 ± 0.19 μM) is also one of the compounds with the highest activity against BChE. In the BChE assay, 2-hydroxybenzaldehyde-based compound 19 (70.11 ± 0.67 μM) indicated the highest activity in comparison to rivastigmine (19.95 ± 0.20 μM). In antioxidant activity studies, the tested molecules showed lower activities than the standard compounds (butylated hydroxytoluene and α-tocopherol). Consequently, some novel compounds can be used as potential inhibitor candidates in future studies.     

Synthesis,characterization, molecular docking studies and in vitro screening of new metal complexes with Schiff base as antimicrobial and antiproliferative agents

A series of Cu(II), Co(II), Pd(II), Pt(II), Zn(II), Cd(II) and Fe(III) complexes were designed and synthesized using Schiff base 1‐phenyl‐2,3‐dimethyl‐4‐(N‐3‐formyl‐6‐methylchromone)‐3‐pyrazolin‐5‐one (HL). The new metal complexes were investigated using various physicochemical techniques including elemental and thermal analyses, molar electric conductivity and magnetic susceptibility measurements, as well as spectroscopic methods. Also, the crystal structures of ligand HL and the Pd(II) complex were determined using single‐crystal X‐ray diffraction analysis. For all compounds, the antimicrobial activity was studied against a series of standard strains: Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis, Escherichia coli, Acinetobacter baumannii, Candida albicans, Candida krusei and Cryptococcus neoformans. The in vitro antiproliferative activity of the ligand and complexes was evaluated against ten cancer cell lines: MSC, A375, B16 4A5, HT‐29, MCF‐7, HEp‐2, BxPC‐3, RD, MDCK and L20B. At 10 μM concentration a significant cytotoxic effect of the Co(II), Pd(II) and Cd(II) complexes was observed against B16 4A5 murine melanoma cells. The Zn(II) complex is active against HEp‐2, RD and MDCK cancer cell lines, where IC₅₀ values vary between 1.0 and 77.6 and for BxPC‐3 the activity index versus doxorubicin is 3.7 times higher.     

Synthesis,structural characterization,antimicrobial, antioxidant and DNA binding studies of some novel homo‐binuclear Schiff base metal (II) complexes

A novel bi‐nucleating Schiff base ligand, 6,6′‐(((1E,1′E)‐thiophene‐2,5‐diylbis (methaneylylidene))bis (azaneylylidene))bis (3,4‐dimethylaniline), and five binuclear M (II) complexes were synthesized. The bi‐nucleating Schiff base ligand and its metal complexes were characterized using various physicochemical techniques, e.g. elemental analyses, spectroscopic methods, conductivity and magnetic moment measurements. The low molar conductance of the complexes in dimethylsulfoxide shows their non‐electrolytic nature. The antibacterial activities were screened against pathogenic bacteria (Staphylococcus aureus, Escherichia coli, Pseudomonas putida and Bacillus subtilis). The antifungal activity was screened against Aspergillus niger, Aspergillus flavus and Rhizoctonia bataicola. The antimicrobial activity data showed that the metal complexes are more potent than the parent Schiff base ligand against microorganisms. The antioxidant activities of the synthesized compounds were investigated through scavenging activity against 2,2‐diphenyl‐2‐picrylhydrazyl, superoxide anion, hydroxyl and 2,2′‐ azinobis (3‐ethylbenzothiazoline‐6‐sulfonic acid) radicals. The complexes have superior radical scavenging activity than the free ligand and the scavenging effects of the Cu (II) complex are stronger than those of the other complexes. DNA binding studies were performed using electronic spectroscopy, fluorometric competition studies and viscosity measurements. The data indicated that there is a marked enhancement in biocidal activity of the ligand under similar experimental conditions because of coordination with metal ions.     

Synthesis,bioevaluation and molecular docking study of new piperazine and amide linked dimeric 1,2,3-triazoles

Abstract

In search of more potent new antitubercular agents, a library of novel piperazine tethered dimeric 1,2,3-triazoles were designed by assembling 1,2,3-triazoles and piperazine in a single molecular architectural framework. The titled compounds (3a–m) were synthesized by 1,3-dipolar cycloaddition of 1,4-di(prop-2-yn-1-yl)piperazine (1) and various azides (2a–m) using click chemistry approach with good yields. All the synthesized compounds (3a–m) have been screened for their in vitro antitubercular, antifungal and antioxidant activities against their respective strains. Among them, 3b, 3d, and 3i have revealed promising antitubercular activity against Mycobacterium tuberculosis (Mtb) H37Rv with MIC 12.5?µg/mL. Molecular docking results provided well-clustered solutions to the mode of binding for these molecules into the active site of Mtb enoyl reductase (InhA). In addition to this, most of synthesized compounds were found to have potential antifungal as well as antioxidant activity.     

Comparative study of the chemical profiling,antioxidant and antimicrobial activities of essential oils of different parts of Thymus willdenowii Boiss & Reut

The analysis of Thymus willdenowii Boiss &; Reut essential oils (TW EOs) shows 33 components accounting for (96.3–97.7%) of all identified. The main constituents of TW EOs were thymol (35.5–47.3%), p-cymene (13.9–23.8%), γ-terpinene (8.9–20.3%). The antioxidant assays revealed that all TW EOs tested showed strong activities, the antimicrobial effect of TW EOs has been tested against isolated clinical strains of Proteus mirabilis (ATCC 35659), Escherichia coli (ATCC 25922), Candida albicans (ATCC 10231), Bacillus cereus (ATCC 10876), and Aspergillus brasilliensis (ATCC 16404). The antimicrobial test indicates that TW EOs show an inhibition effect against all the tested bacteria with a MIC of 6.9 to 27.6 μg/mL^?1. These results proving that the essential oils extracted from Thymus willdenowii Boiss &; Reut may be a new potential source of natural antimicrobial applied in pharmaceutical and food industries.     

Metal complexes of novel Schiff base derived from iron sandwiched organometallic and 4‐nitro‐1,2‐phenylenediamine: Synthesis,characterization, DFT studies,antimicrobial activities and molecular docking

The condensation of 2‐acetylferrocene with 4‐nitro‐1,2‐phenylenediamine in a 1:1 molar ratio, resulting in formation of a novel bi‐dentate organometallic Schiff base ligand (L), (2‐(1‐((2‐amino‐5‐nitrophenyl)imino)ethyl)cyclopenta‐2,4‐dien‐1‐yl)(cyclopenta‐2,4‐dien‐1‐yl)iron. Also, its Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes have been synthesized. The stoichiometric ratios of the prepared compounds were estimated using elemental analysis (C, H, N, M), molar conductivity, FT‐IR, UV‐Vis, ¹H‐NMR, SEM and mass spectral analysis. Furthermore, their TG and DTG properties were studied. The geometrical structure of the complexes was found to be octahedral. From spectral analysis, the Schiff base coordinated to metal ions through the azomethine and amine groups. DFT‐based molecular orbital energy calculations of the synthesized ligand have been studied, in which the ligand was theoretically optimized. The Schiff base and its metal complexes have been screened for their antimicrobial activities against different bacterial and fungal species by using disc diffusion method. The anticancer activities of the ligand and its metal complexes have also been studied towards breast cancer (MCF‐7) and human normal melanocytes (HFB‐4) cell lines. Molecular docking was also used to identify the interaction between the Schiff base ligand and its Cd(II) complex with the active site of the receptors of breast cancer mutant oxidoreductase (PDB ID: 3HB5), crystal structure of Staphylococcus aureus (PDB ID: 3Q8U) and yeast‐specific serine/threonine protein phosphatase (PPZ1) of Candida albicans (PDB ID:5JPE).     

Synthesis,antioxidant and antitumor activities of some of new cyclobutane containing triazoles derivatives

Abstract

Thiosemicarbazides (2a–e) were obtained by the interaction of furan-2-carboxylic acid hydrazide (1) with five different isothiocyanate (RNCS) derivatives. By addition of KOH to the reaction medium, ethyl, allyl, phenyl and benzyl, p-tolyl substituted 1,2,4-triazoles (3a–e) were obtained. 3a–e were dissolved in dry acetone containing K₂CO₃ in the presence of 2-chloro-1-(3-methyl-3-mesitylcyclobutyl) ethanone (4) to give 3,4,5-trisubstituted 1,2,4-triazole sulfanyl compounds containing a cyclobutane ring (5a–e). The structures of the final compounds were confirmed by elemental analyses, FT-IR, ¹H-NMR and ¹³C-NMR. The antioxidant and antitumor properties of the synthesized compounds were also investigated. Three of the triazole derivatives with p-tolyl, benzyl and phenyl substituents (5c–e) displayed good antioxidant and antitumor activity in comparison to the standards.     

Chemical composition,antioxidant, antimicrobial and anticancer activities of the essential oil from the rhizomes of Zingiber striolatum Diels

Abstract

The chemical composition and biological activities of the essential oil (EO) from the rhizomes of Zingiber striolatum Diels were reported for the first time. Forty-five compounds were identified, and represented 95.7% of the total composition of the EO. The predominant components of the EO were β-phellandrene (24.0%), sabinene (17.3%), β-pinene (11.4%), geranyl linalool (8.6%), terpinen-4-ol (8.3%), α-pinene (5.6%) and crypton (4.5%). The EO revealed a weak DPPH and ABTS radical-scavenging activity. The EO exhibited significant antimicrobial activity with the inhibition zones (12.86–24.62?mm) and MIC (0.78–3.12?mg/mL) against Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans. The EO showed significant cytotoxicity against human leukemic (K562), lung cancer (A549) and prostatic carcinoma (PC-3) cell lines with the IC₅₀ values of 29.67, 48.87 and 86.05?μg/mL, respectively. Thus, the EO could be regarded as a bioactive natural product with potential for utilization in the cosmetic and pharmaceutical industry.     

Synthesis and antimicrobial activity evaluation of new dithiocarbamate derivatives bearing thiazole/benzothiazole rings

The synthesis of 2-(substituted phenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A1-A24) derivatives and 2-(4-substituted thiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B1-B14) derivatives was undertaken starting from the potassium salt of 4-(2-pyrimidinyl)piperazine dithiocarbamate. The structures of the obtained compounds were elucidated by ¹H NMR, ¹³C NMR, MS spectral data, and elemental analysis. The antimicrobial activity of the thirty eight newly synthesized compounds were tested against 12 microorganism strains using the microdilution technique. Compounds 2-(4-ethoxycarbonylthiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B12), 2-(3-fluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A18) and 2-(3,4-difluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A21) were determined to possess high antimicrobial activity.     

Antimicrobial and antioxidant activities of a new benzamide from endophytic Streptomyces sp. YIM 67086

A new benzamide (1) and four known compounds (2–5) were isolated from endophytic Streptomyces YIM67086, and their structures were determined as 2-amino-3,4-dihydroxy-5-methoxybenzamide (1), 4-hydroxy-3-methoxybenzoic acid (2), phenylacetic acid (3), N-acetyltyramine (4) and p-hydroxytruxinic acid (5). Compound 5 was first found in the microorganism. The antimicrobial activities of compounds 1–5 and antioxidant activity of compound 1 were investigated.     

Phytochemicals,antioxidant, anti-acetyl-cholinesterase,and antimicrobial activities of decoction and infusion of Pelargonium graveolens

Abstract

In Tunisia, Pelargonium graveolens is widely consumed as a food aromatizing hydrosol. Recent studies have shown the potential of plant solvent-free extracts as food and pharmaceutical natural additives. Accordingly, in this study, we investigate the phenolic content, the volatile fractions of green P. graveolens extracts such as infusion and decoction, and we evaluate their biological activities. The total phenolic content of the infusion (27.05?mg GAE/gDM) is significantly different from that of decoction (31.2?mg GAE/gDM). The GC-MS analysis identified about twenty volatile components in both extracts. The DPPH inhibition and the β-carotene bleaching tests of the infusion and the decoction had considerable results. Besides, infusion and decoction exhibited a relatively high anti-acetyl-cholinesterase activity and a considerable antimicrobial activity against S. aureus, among three tested pathogenic bacteria.