Therapeutic effect of N, N-Diphenyl-1,4-phenylenediamine and adipose-derived stem cells coadministration on diabetic cardiomyopathy in type 1 diabetes mellitus-rat model.

Type 1 diabetes stem-cell-based treatment approach is among the leading therapeutic strategies for treating cardiac damage owing to the stem cells' regeneration capabilities. Mesenchymal stem cells derived from adipose tissue (AD-MSCs) have shown great potential in treating diabetic cardiomyopathy (DCM). Herein, we explored the antioxidant-supporting role of N, N'-diphenyl-1,4-phenylenediamine (DPPD) in enhancing the MSCs' therapeutic role in alleviating DCM complications in heart tissues of type 1 diabetic rats. Six male albinos Wistar rat groups have been designed into the control group, DPPD (250 mg/kg, i.p.) group, diabetic-untreated group, and three diabetic rat groups treated with either AD-MSCs (1 × 106 cell/rat, i.v.) or DPPD or both. Interestingly, all three treated diabetic groups exhibited a significant decrease in serum glucose, HbA1c, heart dysfunction markers (lactate dehydrogenase and CK-MP) levels, and lipid profile fractions (except for HDL-C), as well as some cardiac oxidative stress (OS) levels (MDA, AGEs, XO, and ROS). On the contrary, serum insulin, C-peptide, and various cardiac antioxidant levels (GSH, GST, CAT, SOD, TAC, and HO-1), beside viable cardiac cells (G0/G1%), were markedly elevated compared with the diabetic untreated group. In support of these findings, the histological assay reflected a marked enhancement in the cardiac tissues of all diabetic-treated groups, with obvious excellency of the AD-MSCs + DPPD diabetic-treated group. Such results strongly suggested the great therapeutic potentiality of either DPPD or AD-MSCs single injection in enhancing the cardiac function of diabetic rats, with a great noted enhancement superiority of DPPD and AD-MSCs coadministration.

Multi-target rational design and synthesis of novel diphenyl-tethered pyrazolopyrimidines targeting EGFR and topoisomerase II with potential DNA intercalation and apoptosis induction.

Herein, we envisioned the design and synthesis of novel pyrazolopyrimidines (confirmed by elemental analysis, 1H and 13C NMR, and mass spectra) as multitarget-directed drug candidates acting as EGFR/TOPO II inhibitors, DNA intercalators, and apoptosis inducers. The target diphenyl-tethered pyrazolopyrimidines were synthesized starting from the reaction of phenyl hydrazine and ethoxymethylenemalononitrile to give aminopyrazole-carbonitrile 2. The latter hydrolysis with NaOH and subsequent reaction with 4-chlorobenzaldhyde afforded the corresponding pyrazolo[3,4-d]pyrimidin-4-ol 4. Chlorination of 4 with POCl3 and sequential reaction with different amines afforded the target compounds in good yields (up to 73 %). The growth inhibition % of the new derivatives (6a-m) was investigated against different cancer and normal cells and the IC50 values of the most promising candidates were estimated for HNO97, MDA-MB-468, FaDu, and HeLa cancer cells. The frontier derivatives (6a, 6i, 6k, 6l, and 6m) were pursued for their EGFR inhibitory activity. Compound 6l decreased EGFR protein concentration by a 6.10-fold change, compared to imatinib as a reference standard. On the other side, compounds (6a, 6i, 6k, 6l, and 6m) underwent topoisomerase II (TOPO II) inhibitory assay. In particular, compounds 6a and 6l exhibited IC50s of 17.89 and 19.39 µM, respectively, surpassing etoposide with IC50 of 20.82 µM. Besides, the DNA fragmentation images described the great potential of both candidates 6a and 6l in inducing DNA degradation at lower concentrations compared to etoposide and doxorubicin. Moreover, compound 6l, with the most promising EGFR/TOPO II inhibition and DNA intercalation, was selected for further investigation for its apoptosis induction ability by measuring caspases 3, 7, 8, and 9, Bax, p53, MMP2, MMP9, and BCL-2 proteins. Additionally, molecular docking was used to explain the SAR results based on the differences in the molecular features of the investigated congeners and the target receptors' topology.

Ni-Catalyzed Stereoconvergent Reductive Dimerization of Bromocyclobutenes.

A nickel-catalyzed reductive dimerization of bromocyclobutenes to produce unusual and unprecedented cyclobutene dimers was developed. In a stereoconvergent procedure, various bromocyclobutenes were readily dimerized in good yields, with good diastereoselectivities and broad functional group tolerance. Notably, the presence of a carbonyl group in the starting material appears to dictate diastereoselectivity.

Improving the Durability of Chitosan Films through Incorporation of Magnesium, Tungsten, and Graphene Oxides for Biomedical Applications.

Bacterial infections that cause chronic wounds provide a challenge to healthcare worldwide because they frequently impede healing and cause a variety of problems. In this study, loaded with tungsten oxide (WO3 ), Magnesium oxide (MgO), and graphene oxide (GO) on chitosan (CS) membrane, an inexpensive polymer casting method was successfully prepared for wound healing applications. All fabricated composites were characterized by X-ray powder diffraction (XRD), Fourier transforms infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA). A scanning electron microscope (SEM) was used to study the synthesized film samples' morphology as well as their microstructure. The formed WO3/MgO@CS shows a great enhancement in the UV/VIS analysis with a highly intense peak at 401 nm and a narrow band gap (3.69 eV) compared to pure CS. The enhanced electron-hole pair separation rate is responsible for the WO3/MgO/GO@CS scaffold's antibacterial activity. Additionally, human lung cells were used to determine the average cell viability of nanocomposite scaffolds and reached 121 % of WO3 /MgO/GO@CS nanocomposite, and the IC50 value was found to be 1654 µg/mL. The ability of the scaffold to inhibit the bacteria has been tested against both E. coli and S. aureus. The 4th sample showed an inhibition zone of 11.5±0.5 mm and 13.5±0.5 mm, respectively. These findings demonstrate the enormous potential for WO3 /MgO/GO@CS membrane as wound dressings in the clinical management of bacterially infected wounds.

Corrosion mitigation characteristics of some novel organoselenium thiourea derivatives for acid pickling of C1018 steel via experimental and theoretical study.

Two organoselenium thiourea derivatives, 1-(4-(methylselanyl)phenyl)-3-phenylthiourea (DS036) and 1-(4-(benzylselanyl)phenyl)-3-phenylthiourea (DS038) were produced and categorized using FTIR and NMR (1H and 13C). The effectiveness of the above two compounds as C-steel corrosion inhibitors in molar HCl was evaluated using the potentiodynamic polarization (PD) and electrochemical impedance spectroscopy (EIS) techniques. PD findings indicate that DS036 and DS038 have mixed-type features. EIS results show that growing their dose not only changes the polarization resistance of C-steel from 18.53 to 363.64 and 463.15 Ω cm2 but also alters the double layer capacitance from 710.9 to 49.7 and 20.5 µF cm-2 in the occurrence of 1.0 mM of DS036 and DS038, respectively. At a 1.0 mM dose, the organoselenium thiourea derivatives displayed the highest inhibition efficiency of 96.65% and 98.54%. The inhibitory molecule adsorption proceeded along the Langmuir isotherm on the steel substrate. The adsorption-free energy of the adsorption process was also intended and indicated a combined chemical and physical adsorption on the C-steel interface. FE-SEM studies support the adsorption and protective abilities of the OSe-based molecule inhibitor systems. In Silico calculations (DFT and MC simulations) explored the attraction between the studied organoselenium thiourea derivatives and corrosive solution anions on a Fe (110) surface. The obtained results show that these compounds can make a suitable preventing surface and control the corrosion rate.

Nms-Amides: An Amine Protecting Group with Unique Stability and Selectivity.

p-Toluenesulfonyl (Tosyl) and nitrobenzenesulfonyl (Nosyl) are two of the most common sulfonyl protecting groups for amines in contemporary organic synthesis. While p-toluenesulfonamides are known for their high stability/robustness, their use in multistep synthesis is plagued by difficult removal. Nitrobenzenesulfonamides, on the other hand, are easily cleaved but display limited stability to various reaction conditions. In an effort to resolve this predicament, we herein present a new sulfonamide protecting group, which we term Nms. Initially developed through in silico studies, Nms-amides overcome these previous limitations and leave no room for compromise. We have investigated the incorporation, robustness and cleavability of this group and found it to be superior to traditional sulfonamide protecting groups in a broad range of case studies.

New Strategies for the Functionalization of Carbonyl Derivatives via α-Umpolung: From Enolates to Enolonium Ions.

ConspectusUmpolung, a term describing the reversal of innate polarity, has become an indispensable tool to unlock new chemical space by overcoming the limitations of natural polarity. Introduced by Dieter Seebach in 1979, this principle has had a tremendous impact on synthetic organic chemistry, offering previously inaccessible retrosynthetic disconnections. In contrast to the great progress made over the past decades for the generation of effective acyl anion synthons, the umpolung at the α-position of carbonyls (converting enolates into enolonium ions) has long proved challenging and only recently regained traction. Aiming to develop synthetic approaches to α-functionalization capable of complementing enolate chemistry, our group initiated, nearly 6 years ago, a program devoted to the α-umpolung of carbonyl derivatives. In this Account, following an overview of established methods, we will summarize our findings in this rapidly developing field. We focus on two distinct, yet related, topics of two carbonyl classes: (1) amides, where umpolung is enabled by electrophilic activation, and (2) ketones, where umpolung is enabled using hypervalent iodine reagents. Our group has developed several protocols to allow amide umpolung and subsequent α-functionalization, relying on electrophilic activation. Over the course of our investigations, transformations that are particularly challenging using enolate-based approaches, such as the direct α-oxygenation, α-fluorination, and α-amination of amides as well as the synthesis of 1,4-dicarbonyls from amide substrates, have been unlocked. Based on some of our most recent studies, this method has been shown to be so general that almost any nucleophile can be added to the α-position of the amide. In this Account, special emphasis will be placed on the discussion of mechanistic aspects. It is important to note that recent progress in this area has involved a shift in focus, moving even further away from the amide carbonyl, a development that shall also be detailed in a final subsection that highlights our latest investigations of umpolung-based remote functionalization of the ß- and γ-positions of amides. The second section of this Account covers our more recent work dedicated to the exploration of the enolonium chemistry of ketones, unlocked through the use of hypervalent iodine reagents. By placing our work in the context of previous pioneering achievements, which mainly focused on the α-functionalization of carbonyls, we discuss new skeletal reorganizations of enolonium ions enabled by the unique properties of incipient positive charges α to electron-deficient moieties. Transformations such as intramolecular cyclopropanations and aryl migrations are covered and supplemented by detailed insight into the unusual nature of the intermediate species, including nonclassical carbocations.

Free Amino Group Transfer via α-Amination of Native Carbonyls.

We report herein a straightforward transfer of a free amino group (NH2 ) from a commercially available nitrogen source to unfunctionalized, native carbonyls (amides and ketones) resulting in direct α-amination. Primary α-amino carbonyls are readily produced under mild conditions, further enabling diverse in situ functionalization reactions-including peptide coupling and Pictet-Spengler cyclization-that capitalize on the presence of the unprotected primary amine.

Synthesis and in Silico Investigation of Organoselenium-Clubbed Schiff Bases as Potential Mpro Inhibitors for the SARS-CoV-2 Replication.

Since the first report of the organoselenium compound, ebselen, as a potent inhibitor of the SARS-CoV-2 Mpro main protease by Z. Jin et al. (Nature, 2020), different OSe analogs have been developed and evaluated for their anti-COVID-19 activities. Herein, organoselenium-clubbed Schiff bases were synthesized in good yields (up to 87%) and characterized using different spectroscopic techniques. Their geometries were studied by DFT using the B3LYP/6-311 (d, p) approach. Ten FDA-approved drugs targeting COVID-19 were used as model pharmacophores to interpret the binding requirements of COVID-19 inhibitors. The antiviral efficiency of the novel organoselenium compounds was assessed by molecular docking against the 6LU7 protein to investigate their possible interactions. Our results showed that the COVID-19 primary protease bound to organoselenium ligands with high binding energy scores ranging from -8.19 to -7.33 Kcal/mol for 4c and 4a to -6.10 to -6.20 Kcal/mol for 6b and 6a. Furthermore, the docking data showed that 4c and 4a are good Mpro inhibitors. Moreover, the drug-likeness studies, including Lipinski's rule and ADMET properties, were also assessed. Interestingly, the organoselenium candidates manifested solid pharmacokinetic qualities in the ADMET studies. Overall, the results demonstrated that the organoselenium-based Schiff bases might serve as possible drugs for the COVID-19 epidemic.

Magnesium Ortho-Vanadate/Magnesium Oxide/Graphene Oxide Embedded through Cellulose Acetate-Based Films for Wound Healing Applications.

A multifunctional nano-films of cellulose acetate (CA)/magnesium ortho-vanadate (MOV)/magnesium oxide/graphene oxide wound coverage was fabricated. Through fabrication, different weights of the previously mentioned ingredients were selected to receive a certain morphological appearance. The composition was confirmed by XRD, FTIR, and EDX techniques. SEM micrograph of Mg3(VO4)2/MgO/GO@CA film depicted that there was a porous surface with flattened rounded MgO grains with an average size of 0.31 µm was observed. Regarding wettability, the binary composition of Mg3(VO4)2@CA occupied the lowest contact angle of 30.15 ± 0.8o, while pure CA represents the highest one at 47.35 ± 0.4°. The cell viability % amongst the usage of 4.9 µg/mL of Mg3(VO4)2/MgO/GO@CA is 95.77 ± 3.2%, while 2.4 µg/mL showed 101.54 ± 2.9%. The higher concentration of 5000 µg/mL exhibited a viability of 19.23%. According to optical results, the refractive index jumped from 1.73 for CA to 1.81 for Mg3(VO4)2/MgO/GO@CA film. The thermogravimetric analysis showed three main stages of degradation. The initial temperature started from room temperature to 289 °C with a weight loss of 13%. On the other hand, the second stage started from the final temperature of the first stage and end at 375 °C with a weight loss of 52%. Finally, the last stage was from 375 to 472 °C with 19% weight loss. The obtained results, such as high hydrophilic behavior, high cell viability, surface roughness, and porosity due to the addition of nanoparticles to the CA membrane, all played a significant role in enhancing the biocompatibility and biological activity of the CA membrane. The enhancements in the CA membrane suggest that it can be utilized in drug delivery and wound healing applications.

Design, Synthesis, and Biological Evaluation of Novel Hydroxamic Acid-Based Organoselenium Hybrids.

We report the design and synthesis of novel hydroxamic acid-tethered organoselenium (OSe) hybrids. Their antimicrobial and anticancer activities were assessed against different microbes (e.g., Candida albicans (C. albicans), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus)), as well as liver and breast carcinomas. OSe hybrid 8 showed promising anticancer activity, with IC50 = 7.57 ± 0.5 µM against HepG2 and IC50 = 9.86 ± 0.7 µM against MCF-7 cells. Additionally, OSe compounds 8 and 15 exhibited promising antimicrobial activities, particularly against C. albicans (IA% = 91.7 and 83.3) and S. aureus (IA% = 90.5 and 71.4). The minimum inhibitory concentration (MIC) assay confirmed the potential antimicrobial activity of OSe compound 8. OSe compounds 8 and 16 displayed good antioxidant activities compared to vitamin C in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. These results indicate that hydroxamic acid-based organoselenium hybrids have promising biological activities such as anticancer, antimicrobial, and antioxidant properties, especially compounds 8, 13, 15, and 16, which warrant further studies.

Design, Synthesis, Spectroscopic Inspection, DFT and Molecular Docking Study of Metal Chelates Incorporating Azo Dye Ligand for Biological Evaluation.

A new heterocyclic azo dye ligand (L) was synthesized by the combination of 4-amino antipyrine with 4-aminophenol. The new Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) complexes were synthesized in excellent yields. The metal chelate structures were elucidated using elemental analyses, FT-IR, 1H-NMR, mass, magnetic moment, diffused reflectance spectral and thermal analysis (TG-DTG), and molar conductivity measurement. According to the FT-IR study, the azo dye ligand exhibited neutral tri-dentate behavior, binding to the metal ions with the azo N, carbonyl O, and protonated phenolic OH. The 1H-NMR spectral study of the Zn(II) complex supported the coordination of the zo dye ligand without proton displacement of the phenolic OH. Diffused reflectance and magnetic moment studies revealed the octahedral geometry of the complexes, as well as their good electrolytic nature, excepting the Zn(II) and Cd(II) complexes, which were nonelectrolytes, as deduced from the molar conductivity study. The theoretical calculations of optimized HOMO-LUMO energies, geometrical parameters, electronic spectra, natural atomic charges, 3D-plots of MEP, and vibrational wavenumbers were computed and elucidated using LANL2DZ and 6-311G (d, p) basis sets of density functional theory (DFT) with the approach of B3LYP DFT and TD-DFT methods. The ligand and complexes have been assayed for their antimicrobial activity and compared with the standard drugs. Most of the complexes have manifested excellent antimicrobial activity against various microbial strains. A molecular docking investigation was also performed, to acquire more information about the binding mode and energy of the ligand and its metal complexes to the Escherichia coli receptor using molecular docking. Altogether, the newly created ligand and complexes showed positive antibacterial effects and are worth future study.

Down regulation of fatty acid synthase via inhibition of PI3K/AKT/mTOR in ovarian cancer cell line by novel organoselenium pseudopeptide.

Ovarian cancer (OC) is the 7th most common cancer in women world-wide and the 3rd most common female cancer. For the treatment of OC, there is no successful therapeutic. The medications that are currently available have significant side effects and a low therapeutic index. This work aimed to evaluate the anticancer activity of organoselenium pseudopeptide compound against OC cell lines. After treatment with 50 â€‹µM of compound 4 (CPD 4), the viability was determined. The anticancer activity was further investigated by different methods including cell cycle and apoptosis analysis, colony formation assay, zymography, comet assay and Western blot. In comparison to a positive control, compound 4 showed cytotoxicity toward A2780CP cells rather than A2780 and SKOV-3 â€‹cells. Compound 4 was more selective to OC cells rather than HSF cells. Moreover, Compound 4 was able to inhibit cell migration and proliferation. The anticancer effect of compound 4 was found to be partially via cell cycle arrest, overexpression of p27 â€‹cell cycle inhibitor and induction of apoptosis through DNA fragmentation and activated production of ROS. Compound 4 had a differential effect on the modulation of PI3K/AKT/mTOR signaling pathway in the OC treated cell lines, also inhibited lipogenesis process via downregulation of FASN expression. Conclusion: This work highlights the unique role of Compound 4 against OC via modulation of oxidative stress, inhibition of survival PI3K/AKT/mTOR pathway. Compound 4 was found to be a promising alternative therapy for the treatment of OC in this investigation.

Anticancer, Antimicrobial, and Antioxidant Activities of Organodiselenide-Tethered Methyl Anthranilates.

Novel methyl anthranilate-based organodiselenide hybrids were synthesized, and their chemical structures were confirmed by state-of-the-art spectroscopic techniques. Their antimicrobial properties were assessed against Staphylococcus aureus, Escherichia coli, and Candida albicans microbial strains. Moreover, the antitumor potential was estimated against liver and breast carcinomas, as well as primary fibroblast cell lines. The Staphylococcus aureus and Candida albicans strains were more sensitive than Escherichia coli toward the OSe compounds. Interestingly, methyl 2-amino-5-(methylselanyl) benzoate (14) showed similar antifungal activity to the standard drug clotrimazole (IA% = 100%) and manifested promising antibacterial activity against E. coli (IA% = 91.3%) and S. aureus (IA% = 90.5%). Furthermore, the minimum inhibitory concentration experiments confirmed the antimicrobial activity of the OSe 14, which in turn was comparable to clotrimazole and ampicillin drugs. Interestingly, the anticancer properties were more pronounced in the HepG2 cells. The OSe 14 was the most cytotoxic (IC50 = 3.57 ± 0.1 µM), even more than the Adriamycin drug (IC50 = 4.50 ± 0.2 µM), and with therapeutic index (TI) 17 proposing its potential selectivity and safety. Additionally, OSe compounds 14 and dimethyl 5,5'-diselanediylbis(2-aminobenzoate) (5) exhibited promising antioxidants in the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro assays with 96%, 92%, 91%, and 86% radical scavenging activities compared to 95% by vitamin C in the DPPH and ABTS assays, respectively. These results point to promising antimicrobial, anticancer, and antioxidant activities of OSe 14 and 5 and warrant further studies.

Synthesis, DFT, Biological and Molecular Docking Analysis of Novel Manganese(II), Iron(III), Cobalt(II), Nickel(II), and Copper(II) Chelate Complexes Ligated by 1-(4-Nitrophenylazo)-2-naphthol.

Novelmanganese(II), iron(III), cobalt(II), nickel(II), and copper(II) chelates were synthesized and studied using elemental analysis (EA), infrared spectroscopy, mass spectrometry, ultraviolet-visible spectroscopy, and conductivity, as well as magnetic measurements and thermogravimetric analysis (TG). The azo-ligand 1-[(4-nitrophenyl)diazenyl]-2-naphthol (HL) chelates to the metal ions via the nitrogen and oxygen centers of the azo group and the hydroxyl, respectively. The amounts of H2O present and its precise position were identified by thermal analysis. Density functional theory (DFT) was employed to theoretically elucidate the molecular structures of the ligand and the metal complexes. Furthermore, the quantum chemical parameters were also evaluated. The antimicrobial properties were evaluated against a group of fungal and bacterial microbes. Interestingly, the bioactivity of the complexes is enhanced compared to free ligands. Within this context, the CuL complex manifested the lowest activity, whereas the FeL complex had the greatest. Molecular docking was used to foretell the drugs' binding affinity for the structure of Escherichia coli (PDB ID: 1hnj). Protein-substrate interactions were resolved, and binding energies were accordingly calculated.

The Highly Potent AhR Agonist Picoberin Modulates Hh-Dependent Osteoblast Differentiation.

Identification and analysis of small molecule bioactivity in target-agnostic cellular assays and monitoring changes in phenotype followed by identification of the biological target are a powerful approach for the identification of novel bioactive chemical matter in particular when the monitored phenotype is disease-related and physiologically relevant. Profiling methods that enable the unbiased analysis of compound-perturbed states can suggest mechanisms of action or even targets for bioactive small molecules and may yield novel insights into biology. Here we report the enantioselective synthesis of natural-product-inspired 8-oxotetrahydroprotoberberines and the identification of Picoberin, a low picomolar inhibitor of Hedgehog (Hh)-induced osteoblast differentiation. Global transcriptome and proteome profiling revealed the aryl hydrocarbon receptor (AhR) as the molecular target of this compound and identified a cross talk between Hh and AhR signaling during osteoblast differentiation.

Pumice as a Novel Natural Heterogeneous Catalyst for the Designation of 3,4-Dihydropyrimidine-2-(1H)-ones/thiones under Solvent-Free Conditions.

In this study, pumice is used as a novel natural heterogeneous catalyst for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones/thiones via the one-pot multi-component condensation of aromatic aldehydes, urea/thiourea, and ethyl acetoacetate or acetylacetone in excellent yields (up to 98%). The physical and chemical properties of the catalyst were studied. Their geochemical analysis revealed a basaltic composition. Furthermore, X-ray diffraction showed that it is composed of amorphous materials with clinoptilolite and heulandites zeolite minerals in its pores. Moreover, pumice has a porosity range from 78.2-83.9% (by volume) and is characterized by a mesoporous structure (pore size range from 21.1 to 64.5 nm). Additionally, it has a pore volume between 0.00531 and 0.00781 m2/g and a surface area between 0.053 and 1.47 m2/g. The latter facilitated the reaction to proceed in a short time frame as well as in excellent yields. It is worth noting that our strategy tolerates the use of readily available, cheap, non-toxic, and thermally stable pumice catalyst. The reactions proceeded smoothly under solvent-free conditions, and products were isolated without tedious workup procedures in good yields and high purity. Indeed, pumice can be reused for at least five reuse cycles without affecting its activity.

Unexpected kinetically controlled organoselenium-based isomaleimide: X-ray structure, hirshfeld surface analysis, 3D energy framework approach, and density functional theory calculation.

Reduction of 4,4'-diselanediyldianiline (1) followed by the reaction with bromo-4-(bromomethyl)benzene afforded the corresponding 4-((4-bromobenzyl)selanyl)aniline (2) in 85% yield. N-Maleanilic acid 3 was obtained in 94% yield via the reaction of selenoamine 2 with toxilic anhydride. Subsequent dehydration of N-maleanilic acid 3 using acetic anhydride furnished the unexpected isomaleimide 5-((4-((4-bromophenyl)selanyl)phenyl)imino)furan-2(5H)-one (4) instead of the maleimide 5. The molecular structure of compound 4 was confirmed by mass spectrometry, 1H- and 13C-NMR spectroscopy, and X-ray diffraction analysis. Their cytotoxicity was assessed against two oligodendrocytes, and their respective redox properties were evaluated using 2',7'-dichlorodihydrofluorescein diacetate (H2-DCFDA) assay. Furthermore, their antiapoptotic potential was also evaluated by flow cytometry. The compound crystallizes in triclinic P-1 space group with unit cell parameters a = 5.7880 (4) Å, b = 9.8913 (6) Å, c = 14.5951 (9) Å, V = 1731.0 (3) Å3 and Z = 2. The crystal packing is stabilized by intermolecular hydrogen bonding, π···π, C-Br···π stacking interactions, and other non-covalent interactions. The mapping of different Hirshfeld surfaces and 2D-fingerprint were used to investigate intermolecular interactions. The interaction energies that stabilize the crystal packing were calculated and graphically represented as framework energy diagrams. We present a computational investigation of compound 4's molecular structure at the Density Functional Theory level using the B3LYP method and the 6-31G ++ basis set in this paper. The optimized structure matches the experimental outcome. The global reactivity descriptors and molecular electrostatic potential (M.E.P.) map emphasize the molecule's reactive locations, allowing reactivity prediction. The charge transfer properties of molecules can be estimated by examining Frontier molecular orbitals.

Novel Organoselenium Redox Modulators with Potential Anticancer, Antimicrobial, and Antioxidant Activities.

Novel organic selenides were developed in good yields (up to 91%), and their chemical entities were confirmed by IR, MS, and 1H- and 13C-NMR spectroscopy. Their anticancer and antimicrobial properties were estimated against different human cancer (MCF-7 and HepG2) and healthy (WI-38) cell lines, as well as several microbial strains (Escherichia coli, Staphylococcus aureus, and Candida albicans). Furthermore, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) bioassays were used for the estimation of the antioxidant activities. Generally, cytotoxicity results were more pronounced against the MCF-7 cells than HepG2 cells. Compound 2-((4-((1-hydroxynaphthalen-2-yl)diazenyl)phenyl)selanyl)-N-phenylacetamide (9) was the most cytotoxic, even more than doxorubicin, with IC50 of 3.27 ± 0.2 against 4.17 ± 0.2 µM and twelve-times more selective, respectively. Interestingly, compound 9 exhibited similar antimicrobial potential to reference antibacterial and antifungal drugs and comparable antioxidant activity to vitamin C. These results point to selective cytotoxicity against MCF-7 cells and interesting antimicrobial and antioxidant properties of some newly synthesized organic selenides, which in turn needs further in vitro studies.