Synthesis of 2,4-dihydroxyacetophenone derivatives as potent PDE-1 and -3 inhibitors: in vitro and in silico insights.

Aim: Synthesis of novel bis-Schiff bases having potent inhibitory activity against phosphodiesterase (PDE-1 and -3) enzymes, potentially offering therapeutic implications for various conditions. Methods: Bis-Schiff bases were synthesized by refluxing 2,4-dihydroxyacetophenone with hydrazine hydrate, followed by treatment of substituted aldehydes with the resulting hydrazone to obtain the product compounds. After structural confirmation, the compounds were screened for their in vitro PDE-1 and -3 inhibitory activities. Results: The prepared compounds exhibited noteworthy inhibitory efficacy against PDE-1 and -3 enzymes by comparing with suramin standard. To clarify the binding interactions between the drugs, PDE-1 and -3 active sites, molecular docking studies were carried out. Conclusion: The potent compounds discovered in this study may be good candidates for drug development.

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Structural features and antiproliferative activity of Pd(II) complexes with halogenated ligands: a comparative study between Schiff base and reduced Schiff base complexes.

In order to investigate the structural features and antiproliferative activity of Pd(II) complexes containing halogenated ligands with different flexibility, several Schiff base and reduced Schiff base Pd(II) complexes, namely X1X2PicPd, X1X2PyPd, X1X2Pic(R)Pd, and X1X2Py(R)Pd (where X1 = X2 = Cl, Br and I; Pic: 2-picolylamine; Py = 2-(2-pyridyl)ethylamine), were synthesized and characterized by spectroscopic methods and, in the case of Br2PyPd, Cl2Py(R)Pd and ClBrPy(R)Pd, also by X-ray crystallography. The results of the X-ray crystallography showed that in both series of complexes the Pd(II) ion has a distorted square-planar geometry, although the coordination modes of the two ligands are different. In the Schiff base-type complexes the ligand acts as a tridentate chelate with NN'O donor atoms, whereas in the reduced Schiff base-type complexes the ligand acts as a bidentate chelate with NN' donor atoms. In both series of complexes, the chloride ions occupy the residual coordination sites of the Pd(II) ion. TD-DFT calculations were performed for a better understanding of the UV-Vis spectra. From these calculations it was found that the signal appearing at ∼400 nm in the complexes with reduced Schiff base ligands (X1X2Pic(R)Pd and X1X2Py(R)Pd) is mainly due to a HOMO → LUMO transition, while for the Schiff base complex ClBrPyPd the signal is due to a HOMO → LUMO+1 transition. For the complex I2PicPd, combinations of HOMO-4 → LUMO and HOMO-2 → LUMO transitions were found to be responsible for that signal. In regard to the biological activity profile, all complexes were first investigated as proteasome inhibitors by fluorometric methods. From these enzymatic assays, it emerged that they are good inhibitors with IC50 values in the low-micromolar range and that their inhibitory activity is strictly related to the presence of the metal ion. Subsequently they were also subjected to cell-based assays (the resazurin method) to assess their antiproliferative properties by using two leukemic cell lines, namely the drug-sensitive CCRF-CEM cell line and its multidrug-resistant sub-cell line CEM/ADR5000. In this test they displayed IC50 values in the sub-micromolar and low-micromolar range determined for a selected metal complex (Br2Pic(R)Pd) and ligand (Cl2Pic(R)), respectively. Moreover, docking studies were performed on the two expected molecular targets, i.e. proteasome and DNA, to shed light on the mechanisms of action of these types of Pd(II) complexes.

Insight into the inhibitory potential of metal complexes supported by (E)-2-morpholino-N-(thiophen-2-ylmethylene)ethanamine: synthesis, structural properties, biological evaluation and docking studies.

A thiophene-derived Schiff base ligand (E)-2-morpholino-N-(thiophen-2-ylmethylene)ethanamine was used for the synthesis of M(II) complexes, [TEM(M)X2] (M = Co, Cu, Zn; X = Cl; M = Cd, X = Br). Structural characterization of the synthesized complexes revealed distorted tetrahedral geometry around the M(II) center. In vitro investigation of the synthesized ligand and its M(II) complexes showed considerable anti-urease and leishmanicidal potential. The synthesized complexes also exhibited a significant inhibitory effect on urease, with IC50 values in the range of 3.50-8.05 µM. In addition, the docking results were consistent with the experimental results. A preliminary study of human colorectal cancer (HCT), hepatic cancer (HepG2), and breast cancer (MCF-7) cell lines showed marked anticancer activities of these complexes.

Power of Dopamine: Multifunctional Compound Assisted Conversion of the Most Risk Factor into Therapeutics of Alzheimer's Disease.

In Alzheimer's disease (AD), reactive oxygen species (ROS) plays a crucial role, which is produced from molecular oxygen with extracellular deposited amyloid-ß (Aß) aggregates through the reduction of a Cu2+ ion. In the presence of a small amount of redox-active Cu2+ ion, ROS is produced by the Aß-Cu2+ complex as Aß peptide alone is unable to generate excess ROS. Therefore, Cu2+ ion chelators are considered promising therapeutics against AD. Here, we have designed and synthesized a series of Schiff base derivatives (SB) based on 2-hydroxy aromatic aldehyde derivatives and dopamine. These SB compounds contain one copper chelating core, which captures the Cu2+ ions from the Aß-Cu2+ complex. Thereby, it inhibits copper-induced amyloid aggregation as well as amyloid self-aggregation. It also inhibits copper-catalyzed ROS production through sequestering of Cu2+ ions. The uniqueness of our designed ligands has the dual property of dopamine, which not only acts as a ROS scavenger but also chelates the copper ion. The crystallographic analysis proves the power of the dopamine unit. Therefore, dual exploration of dopamine core can be considered as potential therapeutics for future AD treatment.

Synthesis, Characterization, Antimicrobial and In Silico Studies of Isatin Schiff Base Linked 1,2,3-Triazole Hybrids.

A new series of isatin-Schiff base linked 1,2,3-triazole hybrids has been synthesized using CuAAC approach from (E)-3-(phenylimino)-1-(prop-2-yn-1-yl)indolin-2-one derivatives in high yield (73-91 %). These synthesized derivatives were characterized using FT-IR, 1H NMR, 13C NMR, 2D-NMR and HRMS spectral techniques. The in vitro antimicrobial activity assay demonstrated that most of the tested hybrids exhibited promising activity. Compound 5 j displayed significant antibacterial efficacy against P. aeruginosa and B. subtilis with MIC value of 0.0062 µmol/mL. While, 5 j also showed better antifungal potency against A. niger with MIC value of 0.0123 µmol/mL. The docking studies of most promising compounds were performed with the well-known antibacterial and antifungal targets i. e. 1KZ1, 5TZ1. Molecular modelling investigations demonstrated that hybrids 5 h and 5 l exhibited good interactions with 1KZN and 5TZ1, with binding energies of -9.6 and -11.0 kcal/mol, respectively. Further, molecular dynamics studies of the compounds showing promising binding interactions were also carried out to study the stability of complexes of these hybrids with both the targets.

Dual Antimicrobial-Anticancer Potential, Hydrolysis, and DNA/BSA Binding Affinity of a Novel Water-Soluble Ruthenium-Arene Ethylenediamine Schiff base (RAES) Organometallic.

The need for a systematic approach in developing new metal-based drugs with dual anticancer-antimicrobial properties is emphasized by the vulnerability of cancer patients to bacterial infections. In this context, a novel organometallic assembly was designed, featuring ruthenium(II) coordination with p-cymene, one chlorido ligand, and a bidentate neutral Schiff base derived from 4-methoxybenzaldehyde and N,N-dimethylethylenediamine. The compound was extensively characterized in both solid-state and solution, employing single crystal X-ray diffraction, nuclear magnetic resonance, infrared, ultraviolet-visible spectroscopy, and density functional theory, alongside Hirshfeld surface analysis. The hydrolysis kinetic was thoroughly investigated, revealing the important role of the chloro-aqua equilibrium in the dynamics of binding with deoxyribonucleic acid and bovine serum albumin. Notably, the aqua species exhibited a pronounced affinity for deoxyribonucleic acid, engaging through electrostatic and hydrogen bonding interactions, while the chloro species demonstrated groove-binding properties. Interaction with albumin revealed distinct binding mechanisms. The aqua species displayed covalent binding, contrasting with the ligand-like van der Waals interactions and hydrogen bonding observed with the chloro specie. Molecular docking studies highlighted site-specific interactions with biomolecular targets. Remarkably, the compound exhibited wide spectrum moderate antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, coupled with low micromolar cytotoxic activity against human colorectal adenocarcinoma cells and significant activity against human leukemic monocyte lymphoma cells. The presented findings encourage further development of this compound, promising avenues for its evolution into a versatile therapeutic agent targeting both infectious diseases and cancer.

Structural, dynamic behaviour, in-vitro and computational investigations of Schiff's bases of 1,3-diphenyl urea derivatives against SARS-CoV-2 spike protein.

The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from - 4.73 to - 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate.

Monitoring of singlet oxygen generation of a novel Schiff-base substituted silicon phthalocyanines by sono-photochemical studies and in vitro activities on prostate cancer cell.

This study demonstrates the potential of sono-photodynamic therapy as an effective approach for enhancing singlet oxygen generation using the synthesized Schiff-base diaxially substituted silicon phthalocyanines. In photochemical studies, the singlet oxygen quantum yields (Φ∆) were determined as 0.43 for Si1a, 0.94 for Q-Si1a, 0.58 for S-Si1a, and 0.49 for B-Sia1. In sono-photochemical studies, the Φ∆ values were reached to 0.67 for Si1a, 1.06 for Q-Si1a, 0.65 for S-Si1a, and 0.67 for B-Sia1. In addition, this study demonstrates the therapeutic efficacy of phthalocyanines synthesized as sensitizers on the PC3 prostate cancer cell line through in vitro experiments. The application of these treatment modalities exhibited notable outcomes, leading to a substantial decrease in cell viability within the PC3 prostate cancer cell line. These findings highlight the potential of utilizing these synthesized phthalocyanines as promising therapeutic agents for prostate cancer treatment.

Enhanced selectivity towards melanoma cells with zinc(II)-Schiff bases containing imidazole derivatives.

Zinc(II)-complexes with the general formula [Zn(L)2] containing 8-hydroxyquinoline Schiff bases functionalized with 1-(3-aminopropyl)imidazole or 1-(3-aminopropyl)-2-methyl-1H-imidazole on 2-position and their respective ligands (HL1 or HL2) were synthesized and characterized by NMR, UV-Vis, FTIR and CD spectroscopies as well as ESI-MS spectrometry. Single crystals of HL2 and [Zn(L1)2]n were analysed by SC-XRD. [Zn(L1)2]n shows a 1D polymeric chain structure of alternating Zn(II) cations and bridging Schiff base ligands, in contrast to previously reported monomeric structures of analogous complexes. DFT calculations were performed to rationalize the polymeric X-ray structure of Zn(L1)2. Results showed that the ligands can bind as bi- or tridentate to Zn(II) and there is the possibility of a dynamic behavior for the complexes in solution. Both ligands and complexes present limited stability in aqueous media, however, in the presence of bovine serum albumin the complexes are stable. Molecular docking simulations and circular dichroism spectroscopic studies suggest binding to this protein in close proximity to the Trp213 residue. Biological studies on a panel of cancer cells revealed that the Zn(II)-complexes have a lower impact on cell viability than cisplatin, except for triple-negative breast cancer cells in which they were comparable. Notwithstanding, they display much higher selectivity towards cancer cells vs. normal cells, than cisplatin. They induce the generation of ROS and DNA double-strand breaks, primarily through apoptosis as the mode of cell death. Overall, the novel Zn(II)-complexes demonstrate improved induction of apoptosis and higher selectivity, particularly for melanoma cells, compared to previously reported analogues, making them promising candidates for clinical application.

Hydroxypropyl chitosan/ε-poly-l-lysine based injectable and self-healing hydrogels with antimicrobial and hemostatic activity for wound repair.

The biggest obstacle to treating wound healing continues to be the production of simple, inexpensive wound dressings that satisfy the demands associated with full process of repair at the same time. Herein, a series of injectable composite hydrogels were successfully prepared by a one-pot method by utilizing the Schiff base reaction as well as hydrogen bonding forces between hydroxypropyl chitosan (HCS), ε-poly-l-lysine (EPL), and 2,3,4-trihydroxybenzaldehyde (TBA), and multiple cross-links formed by the reversible coordination between iron (III) and pyrogallol moieties. Notably, hydrogel exhibits excellent physicochemical properties, including injectability, self-healing, water retention, and adhesion, which enable to fill irregular wounds for a long period, providing a suitable moist environment for wound healing. Interestingly, the excellent hemostatic properties of the hydrogel can quickly stop bleeding and avoid the serious sequelae of massive blood loss in acute trauma. Moreover, the powerful antimicrobial and antioxidant properties also protect against bacterial infections and reduce inflammation at the wound site, thus promoting healing at all stages of the wound. The study of biohydrogel with multifunctional integration of wound treatment and smart medical treatment is clarified by this line of research.

Oxidovanadium(V) Schiff Base Complexes Derived from Chiral 3-amino-1,2-propanediol Enantiomers: Synthesis, Spectroscopic Studies, Catalytic and Biological Activity.

Oxidovanadium(V) complexes, [(+)VOL1-5] and [(-)VOL1-5], with chiral tetradentate Schiff bases, which are products of monocondensation of S(‒)-3-amino-1,2-propanediol or R(+)-3-amino-1,2-propanediol with salicylaldehyde derivatives, have been synthesized. Different spectroscopic methods, viz. 1H and 51V NMR, IR, UV-Vis, and circular dichroism, as well as elemental analysis, have been used for their detailed characterization. Furthermore, the epoxidation of styrene, cyclohexene, and two monoterpenes, S(‒)-limonene and (‒)-α-pinene, using two oxidants, aqueous 30% H2O2 or tert-butyl hydroperoxide (TBHP) in decane, has been studied with catalytic amounts of all complexes. Finally, biological cytotoxicity studies have also been performed with these oxidovanadium(V) compounds for comparison with cis-dioxidomolybdenum(VI) Schiff base complexes with the same chiral ligands, as well as to determine the cytoprotection against the oxidative damage caused by 30% H2O2 in the HT-22 hippocampal neuronal cells in the range of their 10-100 µM concentration.

Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide-hydrazone derivatives of 3,4-dihydroxyphenylacetic acid.

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.

Efficient, rapid, and high-yield synthesis of aryl Schiff base derivatives and their in vitro and in silico inhibition studies of hCA I, hCA II, AChE, and BuChE.

This study reports a rapid and efficient synthesis of four novel aryl Schiff base derivatives. Biological activity and molecular modeling studies were conducted to evaluate the inhibitory effects of these compounds on human carbonic anhydrases (hCA) and cholinesterases. The results indicate that the triazole-ring-containing compounds have strong inhibitory effects on hCA I, hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) targets. Besides comparing the Schiff bases synthesized in our study to reference molecules, we conducted in silico investigations to examine how these compounds interact with their targets. Our studies revealed that these compounds can occupy binding sites and establish interactions with crucial residues, thus inhibiting the functions of the targets. These findings have significant implications as they can be utilized to develop more potent compounds for treating the diseases that these target proteins play crucial roles in or to obtain drug precursors with enhanced efficacy.

Zinc(II) Iminopyridine Complexes as Antibacterial Agents: A Structure-to-Activity Study.

Antibiotic resistance is currently a global health emergency. Metallodrugs, especially metal coordination complexes, comprise a broad variety of candidates to combat antibacterial infections. In this work, we designed a new family of Schiff base zinc(II) complexes with iminopyridine as an organic ligand and different inorganic ligands: chloride, nitrate, and acetate. The antibacterial effect of the Zn(II) complexes was studied against planktonic bacterial cells of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) strains. The results showed a moderate biocide activity in both types of planktonic bacteria, which arises from the metal complexation to the Schiff base ligand. Importantly, we confirmed the crucial effect of the metal, with Zn(II) improving the activity of Cu(II) counterparts previously reported. On the other hand, the impact of the inorganic ligands was not significant for the antibacterial effect but was relevant for the complex solubility. Finally, as proof of concept of topical antibacterial formulation, we formulated an emulsion containing the most lipophilic Zn(II) complex and confirmed a sustained release for 24 h in a vertical cell diffusion assay. The promising activity of iminopyridine Zn(II) complexes is potentially worth exploring in more detailed studies.

Schiff bases and their metal complexes to target and overcome (multidrug) resistance in cancer.

Overcoming multidrug resistance (MDR) is one of the major challenges in cancer therapy. In this respect, Schiff base-related compounds (bearing a R1R2CNR3 bond) gained high interest during the past decades. Schiff bases are considered privileged ligands for various reasons, including the easiness of their preparation and the possibility to form complexes with almost all transition metal ions. Schiff bases and their metal complexes exhibit many types of biological activities and are used for the treatment and diagnosis of various diseases. Until now, 13 Schiff bases have been investigated in clinical trials for cancer treatment and hypoxia imaging. This review represents the first collection of Schiff bases and their complexes which demonstrated MDR-reversal activity. The areas of drug resistance covered in this article involve: 1) Modulation of ABC transporter function, 2) Targeting lysosomal ABCB1 overexpression, 3) Circumvention of ABC transporter-mediated drug efflux by alternative routes of drug uptake, 4) Selective activity against MDR cancer models (collateral sensitivity), 5) Targeting GSH-detoxifying systems, 6) Overcoming apoptosis resistance by inducing necrosis and paraptosis, 7) Reactivation of mutated p53, 8) Restoration of sensitivity to DNA-damaging anticancer therapy, and 9) Overcoming drug resistance through modulation of the immune system. Through this approach, we would like to draw attention to Schiff bases and their metal complexes representing highly interesting anticancer drug candidates with the ability to overcome MDR.

Synthesis of new quaternized chitosan Schiff bases and their N-alkyl derivatives as antimicrobial and anti-biofilm retardants in membrane technology.

New quaternized salicylidene chitosan Schiff bases (QSCSBs) and their N-octyl derivatives (OQCs) have been synthesized and characterized, aiming to develop innovative antimicrobial and anti-biofilm agents. This research holds immense potential, as these compounds could be utilized as anti-biofouling additives in membrane technology in the future. The synthesis involved the modification of low molecular-weight-chitosan (LMC) through simultaneous Schiff base formation and quaternization processes to create QSCSBs. Subsequently, QSCSBs were catalytically reduced to form quaternized N-benzyl chitosan (QBCs) intermediates, which then underwent nucleophilic substitution reactions affording N-octyl quaternized chitosans (OQCs). Characterization techniques such as elemental, spectral, and microscopic analyses were used to confirm the successful synthesis of these materials. As membrane technology relies on surface charge, QSCSBs and OQCs with large zeta potentials could be used as positively charged additives. Moreover, SEM image revealed the regular distribution of pores and voids across the additives' surfaces raises intriguing questions about their implications for membrane performance. Meanwhile, the superior antibacterial and antibiofilm potential of these materials, particularly QSCSB2 and OQC2, indicate that the utilization of these compounds as anti-biofouling additives in membrane technology could significantly improve the performance and longevity of membranes used in various applications such as water treatment and desalination.

Synthesis, antimicrobial activity, antioxidant activity and molecular docking of novel chitosan derivatives containing glycine Schiff bases as potential succinate dehydrogenase inhibitors.

Succinate dehydrogenase (SDH) is an important inner mitochondrial membrane-bound enzyme involved in redox reactions during the tricarboxylic acid cycle. Therefore, a series of novel chitosan derivatives were designed and synthesized as potential microbicides targeting SDH and precisely characterized by FTIR, 1H NMR and SEM. Their antifungal and antibacterial activities were evaluated against Botrytis cinerea, Fusarium graminearum, Staphylococcus aureus and Escherichia coli. The bioassays revealed that these chitosan derivatives exerted significant antifungal effects, with four of the compounds achieving 100 % inhibition of Fusarium graminearum merely at a concentration of 0.5 mg/mL. Additionally, CSGDCH showed 79.34 % inhibition of Botrytis cinerea at a concentration of 0.1 mg/mL. In vitro antibacterial tests revealed that CSGDCH and CSGDBH have excellent Staphylococcus aureus and Escherichia coli inhibition with MICs of 0.0156 mg/mL and 0.03125 mg/mL, respectively. Molecular docking studies have been carried out to explore the binding energy and binding mode of chitosan and chitosan derivatives with SDH. The analyses indicated that chitosan derivatives targeted the active site of the SDH protein more precisely, disrupting its normal function and ultimately repressing the growth of microbial cells. Furthermore, the chitosan derivatives were also evaluated biologically for antioxidation, and all of these compounds had a greater degree of reducing power, superoxide radical, hydroxyl radical and DPPH-radical scavenging activity than chitosan. This research has the potential for the development of agricultural antimicrobial agents.

Dual site reactivity of indole-3-Schiff bases with S/Se/Cl substituted ketenes for stereoselective C-4 substituted indole-ß-lactams, biological evaluations, magic chloro effect and molecular docking studies.

A convenient methodology for C-4 indole-ß-lactam hybrids with chloro, sulphur and seleno substitutions through dual site reactivity of indole-3-Schiff bases towards ketenes has been developed. The reaction proceeded in a stereospecific manner with the exclusive formation of trans-ß-lactams assigned with respect to C3-H and C4-H. The synthesized novel ß-lactams have been characterized with the help of elemental analysis (CHNS) and spectroscopic techniques viz.1H NMR, 13C NMR, DEPT 135, HSQC and IR. The trans configuration was further estabilished based on X-ray crystallographic data. Examination of antibacterial properties unveiled that only derivatives 5a and 5b, featuring chloro substitution, exhibited potent activities, underscoring the emergence of the recently coined term "magic chloro effect". Molecular docking analysis provided additional support for the observed in vitro antibacterial activities of compounds 5a-b.

New penta-Coordinated Cadmium(II) Complexes: Synthesis, Characterization, Thermal, Antimicrobial, Antioxidant and Cytotoxicity Properties.

In this paper, a new tridentate Schiff base ligand (L) with nitrogen donor atoms and its cadmium(II) complexes with the general formula of CdLX2 (X=Cl-, Br-, I-, SCN-, N3 -, NO3 -) have been synthesized and characterized by physical and spectral (FT/IR, UV-Vis, Mass, and 1H, 13C NMR spectroscopies) methods. Also nano-structured cadmium chloride and bromide complexes were synthesized by sonochemical method and then used to prepare nanostructured cadmium oxide confirmed by XRD and SEM techniques. Thermal behavior of the compounds was studied in the temperature range of 25 to 900 °C under N2 atmosphere at a heating rate of 20 °C/ min. Moreover, thermo-kinetic activation parameters of thermal decomposition steps were calculated according to the Coats-Redfern relationship. Antimicrobial activities of the synthesized compounds against two gram-positive and two gram-negative bacteria such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and two fungi of Candida albicans and Aspergillus niger were investigated by well diffusion method. SEM technique was used to monitor the morphological changes of the bacteria treated with the compounds. The 2,2-Diphenyl-1-picrylhydrazyl(DPPH) and the ferric reducing antioxidant power (FRAP) methods were used to evaluate the antioxidant ability of the ligand and its cadmium(II) complexes. In final, the cytotoxicity properties of the ligand and some cadmium(II) complexes against PC3 cancer cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) bioassay and nitric oxide (NO) level measurement. The morphological changes of prostate cancer (PC3) cells due to treatment with the ligand and its complexes confirmed their anticancer effectiveness.

1,2,3-triazole and chiral Schiff base hybrids as potential anticancer agents: DFT, molecular docking and ADME studies.

A series of novel 1,2,3-triazole and chiral Schiff base hybrids 2-6 were synthesized by Schiff base condensation reaction from pre-prepared parent component of the hybrids (1,2,3-triazole 1) and series of primary chiral amines and their chemical structure were confirmed using NMR and FTIR spectroscopies, and CHN elemental analysis. Compounds 1-6 were evaluated for their anticancer activity against two cancer PC3 (prostate) and A375 (skin) and MRC-5 (healthy) cell lines by Almar Blue assay method. The compounds exhibited significant cytotoxicity against the tested cancer cell lines. Among the tested compounds 3 and 6 showed very good activity for the inhibition of the cancer cell lines and low toxicity for the healthy cell lines. All the compounds exhibited high binding affinity for Androgen receptor modulators (PDB ID: 5t8e) and Human MIA (PDB ID: 1i1j) inhibitors compared to the reference anticancer drug (cisplatin). Structure activity relationships (SARs) of the tested compounds is in good agreement with DFT and molecular docking studies. The compounds exhibited desirable physicochemical properties for drug likeness.