Phenyl Research Articles

Development of the detailed mechanism of pyrolysis and combustion of triphenyl phosphate: New quantum chemistry calculations and experimental data on structure of the H2/O2/Ar flame doped with TPP

A possible method for a flammability reduction of the polymeric materials is the introduction of flame retardants into their composition. An effective search for optimal flame retardants and an understanding of their inhibition mechanisms requires the extensive information on the chemistry of their transformation in flames. A new data on chemical flame structure of a premixed H2/O2/Ar flame doped with 1000 ppm of triphenyl phosphate (TPP) at a pressure of 1 atm was obtained with a molecular-beam mass-spectrometry technique. Among intermediate products of the TPP decomposition were identified: several large phosphorus containing compounds, small phosphorus containing species (PO, PO2, HOPO, HOPO2), cyclic hydrocarbons (benzene, toluene, phenol), phenyl and phenoxy radicals. The detailed kinetic mechanism proposed earlier for the thermal degradation of TPP was updated with several new reactions including reactions with common flame radicals H/OH/CH3. Reaction rate constants were calculated using the Rice-Ramsberger-Kassel-Marcus theory and potential energy surfaces obtained by the DLPNO-CCSD(T)/cc-pVQZ//ωb97xd/6-31G(d) method. A comparison between experimental data and simulation results with the new model has shown a satisfactory qualitative and quantitative agreement, which confirmed that, the TPP decomposition occurs in flame according to the proposed scheme.

Metal–carbene-guided twofold cross-coupling of ethers with chromium catalysis

Coupling by metal–carbene transfer enables the formation of several different bonds at the carbenoid site, enabling prochiral Csp3 centers that are fundamental three-dimensional substructures for medicines to be forged with increased efficiency. However, strategies using bulk chemicals are rare because of the challenge of breaking two unactivated geminal bonds. Herein, we report the reactivity of ethers to form metal–carbene intermediate by cleavage of α-Csp3–H/Csp3–O bonds, which achieve selective coupling with arylmagnesium bromides and chlorosilanes. These couplings are catalysed by cyclic (alkyl)(amino)carbene-chromium complex and enable the one-step formation of 1,n-arylsilyl alcohols and α-arylated silanes. Mechanistic studies indicate that the in-situ formed low-valent Cr might react with iodobenzene to form phenyl radical species, which abstracts the α-H atom of ether in giving α-oxy radical. The latter combines with Cr by breaking α-Csp3–O bond to afford metal–carbene intermediate, which couples with aryl Grignard and chlorosilane to form two σ-bonds.

Boosting Organic Solar Cells to Over 18% Efficiency through Dipole-Dipole Interactions in Fluorinated Nonfused Ring Electron Acceptors.

This study successfully designed and synthesized two nonfused ring electron acceptors, 412-6F and 412-6Cl, modified with fluorine and chlorine substituents, respectively. Single-crystal analysis revealed that 412-6F possesses a planar molecular backbone and exhibits pronounced dipole-dipole interactions between the fluorine atoms on the lateral phenyl groups and the carbonyl oxygen atoms on the end groups. This specific interaction promotes dense end-group stacking, leading to a reduced interlayer spacing. Improved crystallinity and coherence length are observed in the D18:412-6F blend film. Conversely, 412-6Cl adopts a more distorted configuration and lacks these interactions. As a result, the organic solar cell (OSC) based on D18:412-6F achieved a remarkable power conversion efficiency of 18.03%, surpassing the performance of the D18:412-6Cl OSC. This underscores the importance of designing novel acceptors with beneficial intermolecular interactions to enhance OSC efficiency, thus providing a new direction for organic photovoltaic advancement.

Formulation and evaluation of dosage form of fast dissolving oral film of Rofecoxib

Rofecoxib is utilized for the treatment of osteoarthritis, rheumatoid joint inflammation, intense torment in grown-ups, and essential dysmenorrhea, just as intense therapy of headache assaults with or without emanations. Rofecoxib is strong. This compound has a place with the stilbenes. These are natural mixes containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are acquired from the normal phenylpropene (C6-C3) skeleton building block. The presentation of at least one hydroxyl gathering to a phenyl ring leads to stilbenoids. Rofecoxib has a half-existence of 17 hours and its mean oral bioavailability at restoratively suggested dosages of 125,25,and 50 mg is roughly 93%. The proteins that rofecoxib target incorporate elastin and prostaglandin G/H synthase Cytochrome P4501A2, Cytochrome P4503A4, Cytochrome P4502C9, Cytochrome P4502C8, and Prostaglandin G/H synthase1 are known to processor of Rofecoxib. Rofecoxib oral thin films were prepared from the evaluation studies RCX2 with 98.14% drug release is considered as the optimized formulation.

Theoretical study of the antioxidant mechanism and structure-activity relationships of 1,3,4-oxadiazol-2-ylthieno[2,3-d]pyrimidin-4-amine derivatives: a computational approach

A theoretical thermodynamic study was conducted to investigate the antioxidant activity and mechanism of 1,3,4-oxadiazol-2-ylthieno[2,3-d]pyrimidin-4-amine derivatives (OTP) using a Density Functional Theory (DFT) approach. The study assessed how solvent environments influence the antioxidant properties of these derivatives. With the increasing prevalence of diseases linked to oxidative stress, such as cancer and cardiovascular diseases, antioxidants are crucial in mitigating the damage caused by free radicals. Previous research has demonstrated the remarkable scavenging abilities of 1,3,4-oxadiazole derivatives, prompting this investigation into their potential using computational methods. DFT calculations were employed to analyze key parameters, including bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), and electron transfer enthalpy (ETE), to delineate the antioxidant mechanisms of these compounds. Our findings indicate that specific electron-donating groups such as amine on the phenyl rings significantly enhance the antioxidant activities of these derivatives. The study also integrates global and local reactivity descriptors, such as Fukui functions and HOMO-LUMO energies, to predict the stability and reactivity of these molecules, providing insights into their potential as effective synthetic antioxidants in pharmaceutical applications.

Rotational Spectroscopy as a Tool to Characterize Sweet Taste: The Study of Dulcin.

According to old theories of sweetness, the perception of sweet substances is closely linked to the arrangement of atoms within them. To assess the validity of these theories, we conducted an analysis of the structure of the artificial sweetener dulcin for the first time, utilizing microwave spectroscopy and a laser ablation source. These techniques have enabled the identification of two conformers, which are stabilized by an intramolecular hydrogen bond between the amino group and the phenyl ring. The observed conformations were examined in light of the Shallenberger-Acree-Kier molecular theory of sweet taste, and they align with the hypothesized criteria. Furthermore, the study illustrates how conformational relaxation can alter the equilibrium conformational distribution, resulting in the absence of certain conformers in the conformational landscape.

Synthesis, evaluation and structure-activity relationship studies of pterodontic acid acylated derivatives with anti-flu A virus (H1N1) activity in vitro

In order to develop antiviral drugs, we utilized pterodontic acid (Poa-1) as a lead compound and conducted various modifications, including oxidation, reduction, addition, esterification, and acylation, resulting in the synthesis of 29 derivatives, of which 25 were novel acylation derivatives. Cell-level validation demonstrated that 4 derivatives exhibited significant inhibitory effects on the influenza A virus (H1N1), with an IC50 = 4.04–36.13 μM. Notably, four acylation derivatives (compounds IIE5, IIE6, IIE9, and IIE17) exhibited specific antiviral activities against influenza A virus (H1N1) with low cytotoxicity, indicating favorable therapeutic indices (SI = 3.5–11.9). Structure-activity relationship studies indicated that C5–C6 olefins are essential groups for antiviral activity, C11–C12 conjugated olefins will not interfere with antiviral activity. Carboxylic acid is an essential group for activity. Moreover，Carboxylic acid acylation can improve antiviral activity, and the inclusion of guanidine, cyclic amine, and phenyl groups with electron-donating substituents could enhance the antiviral activity of the lead compound. Natural products structural modifications are capable of improving the biological activity of lead compounds, offering a rapid pathway for the development of potent new structures.

Helmet-Roled Molecules Carrying Double Metronidazole Frameworks and Phenyl Ring for Strengthening Adsorption and Anticorrosion on Mild Steel.

This study prepared new helmet-roled molecules (HMs) carrying metronidazole frameworks and a phenyl ring for strengthening adsorption and anticorrosion on mild steel. The adsorption of the HMs on the copper surface was understood by material simulation computation. Furthermore, the surface analysis experiments suggest that the studied molecules could be adsorbed to a mild steel surface through the chemical coordination bonding. The remarkable corrosion resistance of the HMs for mild steel in HCl was surveyed by potentiodynamic polarization and electrochemical impedance spectroscopy at 298 K. The HMs including two metronidazole skeletons displayed the stronger corrosion inhibition effect on mild steel than the HM1 bearing one single metronidazole part (the corrosion inhibition efficiency, HM3, 98.03%, HM2, 95.14%, HM1, 88.72%). The results presented in this study provided an efficient strategy to develop new clinical medicine-based corrosion inhibitors for metal in acid medium through molecular preconstruction.

Synthesis, photophysics and two-photon absorption of imidazole-centred tripodal chromophores.

Tripodal push-pull chromophores with D-(π-A)3 arrangement were synthesized using 1-methyl-2,4,5-triphenyl-1H-imidazole as a central electron donor, and their thermal, electrochemical, photophysical and non-linear optical properties were studied and corroborated with quantum-chemical calculations. Their facile synthesis involved Suzuki-Miyaura and Knoevenagel reactions, allowing the installation of various peripheral electron acceptors such as formyl, cyano, ester, trifluoromethyl and more complex moieties such as malonic/acetic acid derivatives, indan-1,3-dione and rhodanine. All phenyl rings appended at the central imidazole core were more or less twisted depending on the peripheral substitution. Although imidazole undergoes reversible one-electron oxidation, peripheral acceptors are reduced irreversibly in a multi-electron process. This behaviour is further seen as a variation of the LUMO, while the HOMO remained almost unaltered across the whole series. TD-DFT calculations revealed centrifugal charge transfer from the central imidazole to all C2, C4 and C5 branches occupied by the LUMO, LUMO+1 and LUMO+2. The HOMO-LUMO gap is tuneable within the range of 3.55-2.31 eV, while the longest-wavelength absorption/emission maxima were found within the broad range of 304-448/393-612 nm. Although the absorption spectra are solvent-independent, the emission depends strongly on the solvent polarity and the electron-withdrawing power of the peripheral acceptors. Extended chromophores with complex electron acceptors were investigated as two-photon absorbers, revealing relatively good cross-section values of up to 521 GM and a figure-of-merit (ΦF × δ2PA) of around 190 GM.

Synergistic Photocatalysis by α-MoO3 Nanostructures and SWCNT Nanocomposites for Efficient Cross-Linking and Oxidative Degradation of Polystyrene Nanoplastics.

Nanoplastics (NPs) generated from plastic debris weathering pose a significant threat to ecosystems. The ubiquity of plastics driven by their advantageous physical properties, necessitates the development of efficient degradation and removal methods. Polystyrene (PS), a common and hazardous aquatic NP is a long-chain hydrocarbon with alternating phenyl groups. This study investigates the photooxidative degradation of PS NPs under UV light irradiation using synthesized MoO3 nanoflakes, nanobelts, and MoO3/SWCNT nanocomposites. Raman spectroscopy, X-ray diffraction, atomic force microscopy, high-resolution transmission electron microscopy, energy dispersive X-ray, Brunauer-Emmett-Teller, and UV-vis spectroscopy were employed to characterize the photocatalyst. Field emission scanning electron microscopy was used to visualize morphological changes in the spherical PS NPs upon interaction with the photocatalysts. MoO3 nanoflakes acting as a photocatalyst under UV irradiation for 24 h achieved an impressive degradation efficiency exceeding 19%. This treatment significantly reduced the average diameter of PS NPs from 220 to 178 nm. Notably, even higher degradation efficiencies were observed with MoO3 nanobelts and nanocomposites as a complete change in the spherical morphology of PS NPs is observed. Fourier transform infrared spectroscopy elucidated the chemical transformations of PS during degradation. The observed changes in PS NPs structure due to photocatalytic oxidation at different time intervals indicate a promising approach.

Computational Design and Experimental Validation of an Orthogonal X-bond/H-bond System to Improve the Binding Affinity and Recognition Specificity between Anesthetic Protein Kinase Cι and its Pseudosubstrate Peptide

Protein kinase C isoform [Formula: see text] (PKC[Formula: see text]) is an essential regulator of diverse neurobiological signaling pathways, which has been implicated in general anesthetic action and a variety of nervous neoplasms. Traditional efforts have been primarily addressed on the development of small-molecule inhibitors to target the catalytic or regulatory domain of this kinase. Instead, we herein reported a rational chemical modification of Par3 pseudosubstrate peptide to target the kinase domain with improved affinity and specificity. Structural and energetic analysis suggested that the Par3 peptide can be divided into two binding-independent sections; they are separately anchored to the substrate-binding pocket of PKC[Formula: see text] with two aromatic anchor residues Phe818 and Phe823. The side-chain phenyl group of these two aromatic residues was systematically substituted by different halogen moieties at [Formula: see text]-, [Formula: see text]- and [Formula: see text]-positions of the phenyl group. It is revealed that the [Formula: see text]-bromination of Par3 Phe818 and the [Formula: see text]-iodinization of Par3 Phe823 residue can separately form two geometrically and energetically satisfactory orthogonal halogen (X)-bond/hydrogen (H)-bond [ortX/H] motifs across Par3 complex interface with PKC[Formula: see text]; they co-define a so-called ortX/H system and were demonstrated to improve both the binding affinity and recognition specificity of the kinase–peptide interaction by integrating in silico analysis and in vitro assay. The peptide affinity promotes 23.5-fold and 6.6-fold upon the formation of ortX/H motif-I and motif-II, respectively, which further increases to 43.5-fold by forming the complete ortX/H system, indicating cooperativity between the two motifs in the system. In addition, we also demonstrated that the ortX/H system can considerably enhance the peptide selectivity for its cognate PKC[Formula: see text] and noncogante isoforms PKC[Formula: see text] and PKC[Formula: see text].

Nucleophilic Aromatic Substitution of Halobenzenes and Phenols with Catalysis by Arenophilic π Acids.

ConspectusLewis π acids, particularly high-valent transition metals with vacant orbitals, can coordinate with unsaturated compounds such as alkynes and alkenes by means of π-bonding. The coordination enhances the electrophilicity of the bound compounds, thereby facilitating reactions─such as nucleophilic addition─that take place at the ligated carbon-carbon multiple bonds. This activation phenomenon occurs at the ligand rather than at the metal atom, and it has been extensively utilized in the development of catalytic methods. In addition to alkynes and alkenes, aromatic compounds featuring a phenyl ring can be activated by an electrophilic transition-metal unit (e.g., Cr(CO)3, [Mn(CO)3]+, [CpFe]+, or [CpRu]+, where Cp = cyclopentadienyl) through π coordination. Over the past several decades, remarkable advances have been achieved in the development of reactions occurring on bound arenes, capitalizing on the highly electron-withdrawing nature of these transition-metal units and on the thermodynamic stability of η6-arene complexes. A prime example is the extension of nucleophilic aromatic substitution (SNAr) reactions to electron-neutral and -rich halobenzenes. Such arenes, which are normally inert to classical SNAr, can undergo sequences involving complex formation, substitution, and complex decomposition. Despite the successes achieved through the utilization of preformed complexes, the application of reversible arene coordination to catalytic systems has seen only limited progress. Consequently, in π-coordination activation, transition-metal units are commonly considered to be components of bound arene complexes rather than π-acid catalysts.In this Account, we summarize our recent research on catalytic SNAr reactions of halobenzenes and phenols enabled by reversible π-coordination of the arenes with electrophilic Ru or Rh catalysts, which we refer to as arenophilic π-acids. First, we developed a method for SNAr amination of fluorobenzenes with catalysis by a Ru(II) complex with a hemilabile P,O-bidentate ligand. The use of the hemilabile ligand significantly enhanced catalytic efficiency, allowing electron-rich and -neutral arenes to undergo amination without the need of excess fluorobenzenes. In a subsequent study of hydroxylation and alkoxylation reactions, we found that Rh(III) catalysts bearing a Cp-type ligand had a substantial activating effect. In addition, by isolating an η5 complex as the reaction intermediate, we obtained evidence in support of the long-standing hypothesis that SNAr of η6-arene complexes proceeds via a stepwise mechanism. Next, we extended the Rh-catalyzed SNAr to chloro- and bromobenzenes, which are abundant and readily available but are less reactive than corresponding fluorides toward SNAr. When the weakly nucleophilic alcohol hexafluoroisopropanol was used as a reaction partner, we were able to synthesize hexafluoroisopropyl aryl ethers, which are challenging to obtain by means of conventional approaches. Beyond halobenzenes, we successfully applied π-coordination strategy to achieve umpolung substitution reactions of phenols, which are typically nucleophilic. We found that an arenophilic Rh or Ru catalyst activated the phenol ring by π coordination instead of κ-O coordination, generating transient η5-phenoxo complexes that subsequently underwent carbonyl-amine condensation to produce anilines without the need for an exogenous oxidant or reductant. We anticipate that our research on catalyst development and reactions involving π-coordination activation will facilitate further advances in the application of arenophilic π acids.

Understanding the gelation properties of the fluorophenyl glycosides of arabinoside gelators: experimental and theoretical studies.

In supramolecular gelation, fluorinated gelators are important due to the unique properties displayed by these compounds that arise out of the presence of fluorine atoms. Generally, incorporation of fluorine leads to higher mechanical strength of the gels compared to their non-fluorinated counterparts and this property is enhanced with increasing the number of fluorine atoms. Herein, we show that the incorporation of fluorine into the phenyl ring of phenyl arabinoside allows the molecule to act as a gelator, unlike the non-fluorinated compound. We also show that the mechanical strength and stiffness of the gels is not only dependent on the positions of the fluorine atoms but also guided by their number. Detailed experimental studies, supported by computational studies, allowed us to rationalize the observed supramolecular interactions and propose reasons based on the conformational preferences of these compounds that allow additional hydrogen bonds and π-π interactions which guide the self-assembly, in addition to the primary H-bonding interactions. This, in turn, affects the mechanical behavior of these gels.

Investigation of the molecular structure of CHBP, biological activities and SARS-CoV-2 protein binding interaction by molecular and biomolecular spectroscopy approaches

The objective of this investigation is to learn more about the structural, electrical, spectroscopic, and physiochemical characteristics of biologically active cyano-4′-hydroxybiphenyl (CHBP). The title molecule’s optimized conformational analysis was computed using the DFT/B3LYP/6–311++G (d, p) level of theory. The observed wavenumbers were compared with theoretical FT-IR and FT-Raman spectra. 1H and 13C NMR experimental spectra in CDCl3 solution (solvent phase) were recorded and the chemical shift was calculated. NBO analysis was used to examine the transfer of charge as well as the intermolecular and intramolecular bonding of orbitals. The TD-DFT (time-dependent DFT) approach was used to estimate theoretical values for both the gas and solvent (ethanol) in the corresponding transitional research, which was conducted using UV–Vis’s spectra. Energy gap (Eg = 0.26764 eV) implies that the strong potential for charge transfer, and the stability of the CHBP compound. CHBP compound’s has bioactive nature, its drug-likeness and biological properties were evaluated. The predicted topological polar surface area of 44.02 \\AA2 for the molecule falls within the permissible range of < 140 \\AA2. Based on the docking results, the most stable docking score value is −6.84 kcal/mol. In that interaction, MET 165 affects both phenyl rings in a pi-sulphur fashion and a single bond hydrogen with protein moieties GLN 192. This suggests that the pi-alkyl in PRO 168 is a hydroxyl substitutional ring. Our findings demonstrate the CHBP compound is a good inhibitor against the SAR COVID-19 viral protein.

Revival of Degraded CsPbI3 Nanocrystals by Diselenide Ligand and Nanocrystal Self-Assembly on Nanofibrilar Ligand Template.

Among the lead halide perovskite (LHP) family, CsPbI3 is known to be significantly vulnerable to moisture, which hinders its use in real device applications. It is reported that chalcogen-based ligands can better stabilize CsPbI3 and revive nanocrystals (NCs). Here, diphenyl diselenide (DPhDSe) ligand is used to revive the degraded CsPbI3 NCs through a post-synthetic treatment of adding a small amount of DPhDSe in the degraded NC dispersion. DPhDSe in the dispersion formed nanofibrillar crystals at a low temperature through the π-π stacking of the phenyl ring. The nanofibrils played as a template on which the NCs self-assembled and they are attached side-by-side to form microfibers. The microfiber powder containing the NCs is optically stable at ambient conditions and morphologically self-healable by mild thermal annealing due to the dynamic Se─Se bond. The mechanism of the structural changes, optical transitions, and chemical changes has been systematically characterized through electron microscopy, diffraction, spectroscopy, and elemental analysis.

Synthesis, molecular and crystal structures of 4-amino-3,5-difluorobenzonitrile, ethyl 4-amino-3,5-difluorobenzoate, and diethyl 4,4′-(diazene-1,2-diyl)bis(3,5-difluorobenzoate)

The crystal structures of two intermediates, 4-amino-3,5-difluorobenzonitrile, C7H4F2N2 (I), and ethyl 4-amino-3,5-difluorobenzoate, C9H9F2NO2 (II), along with a visible-light-responsive azobenzene derivative, diethyl 4,4′-(diazene-1,2-diyl)bis(3,5-difluorobenzoate), C18H14F4N2O4 (III), obtained by four-step synthetic procedure, were studied using single-crystal X-ray diffraction. The molecules of I and II demonstrate the quinoid character of phenyl rings accompanied by the distortion of bond angles related to the presence of fluorine substituents in the 3 and 5 (ortho) positions. In the crystals of I and II, the molecules are connected by N—H...N, N—H...F and N—H...O hydrogen bonds, C—H...F short contacts, and π-stacking interactions. In crystal of III, only stacking interactions between the molecules are found.

Exploring a New Generation of Pyrimidine and Pyridine Derivatives as Anti-Influenza Agents Targeting the Polymerase PA-PB1 Subunits Interaction.

The limited range of available flu treatments due to virus mutations and drug resistance have prompted the search for new therapies. RNA-dependent RNA polymerase (RdRp) is a heterotrimeric complex of three subunits, i.e., polymerase acidic protein (PA) and polymerase basic proteins 1 and 2 (PB1 and PB2). It is widely recognized as one of the most promising anti-flu targets because of its critical role in influenza infection and high amino acid conservation. In particular, the disruption of RdRp complex assembly through protein-protein interaction (PPI) inhibition has emerged as a valuable strategy for discovering a new therapy. Our group previously identified the 3-cyano-4,6-diphenyl-pyridine core as a privileged scaffold for developing PA-PB1 PPI inhibitors. Encouraged by these findings, we synthesized a small library of pyridine and pyrimidine derivatives decorated with a thio-N-(m-tolyl)acetamide side chain (compounds 2a-n) or several amino acid groups (compounds 3a-n) at the C2 position. Interestingly, derivative 2d, characterized by a pyrimidine core and a phenyl and 4-chloro phenyl ring at the C4 and C6 positions, respectively, showed an IC50 value of 90.1 μM in PA-PB1 ELISA, an EC50 value of 2.8 μM in PRA, and a favorable cytotoxic profile, emerging as a significant breakthrough in the pursuit of new PPI inhibitors. A molecular modeling study was also completed as part of this project, allowing us to clarify the biological profile of these compounds.

Design, Synthesis, and Characterization of Novel Thiazolidine-2,4-Dione-Acridine Hybrids as Antitumor Agents.

This study focuses on the synthesis and structural characterization of new compounds that integrate thiazolidine-2,4-dione, acridine moiety, and an acetamide linker, aiming to leverage the synergistic effects of these pharmacophores for enhanced therapeutic potential. The newly designed molecules were efficiently synthesized through a multi-step process and subsequently transformed into their hydrochloride salts. Comprehensive spectroscopic techniques, including nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), infrared (IR) spectroscopy, and elemental analysis, were employed to determine the molecular structures of the synthesized compounds. Biological evaluations were conducted to assess the therapeutic potential of the new compounds. The influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC50 values determined via MTT assays. An in-depth analysis of the structure-activity relationship (SAR) revealed intriguing insights into their cytotoxic profiles. Compounds with electron-withdrawing groups generally exhibited lower IC50 values, indicating higher potency. The presence of the methoxy group at the linking phenyl ring modulated both the potency and selectivity of the compounds. The variation in the acridine core at the nitrogen atom of the thiazolidine-2,4-dione core significantly affects the activity against cancer cell lines, with the acridin-9-yl substituent enhancing the compounds' antiproliferative activity. Furthermore, compounds in their hydrochloride salt forms demonstrated better activity against cancer cell lines compared to their free base forms. Compounds 12c·2HCl (IC50 = 5.4 ± 2.4 μM), 13d (IC50 = 4.9 ± 2.9 μM), and 12f·2HCl (IC50 = 4.98 ± 2.9 μM) demonstrated excellent activity against the HCT116 cancer cell line, and compound 7d·2HCl (IC50 = 4.55 ± 0.35 μM) demonstrated excellent activity against the HeLa cancer cell line. Notably, only a few tested compounds, including 7e·2HCl (IC50 = 11.00 ± 2.2 μM), 7f (IC50 = 11.54 ± 2.06 μM), and 7f·2HCl (IC50 = 9.82 ± 1.92 μM), showed activity against pancreatic PATU cells. This type of cancer has a very high mortality due to asymptomatic early stages, the occurrence of metastases, and frequent resistance to chemotherapy. Four derivatives, namely, 7e·2HCl, 12d·2HCl, 13c·HCl, and 13d, were tested for their interaction properties with BSA using fluorescence spectroscopic studies. The values for the quenching constant (Ksv) ranged from 9.59 × 104 to 10.74 × 104 M-1, indicating a good affinity to the BSA protein.

Design, synthesis and evaluation of new methyl piperazine derivatives as anticancer agents

BackgroundTo overcome the problem of side effects and toxicity, development of new anticancer agents is needed. Recently, piperidine salicylanilide derivatives with nanomolar epidermal growth factor receptor (EGFR) inhibitory and cytotoxicity activity have been reported. In the present study effect of replacing piperidine in reported piperidine salicylanilide with N-methyl piperazine and changing substituent’s of phenyl ring at other end on anticancer activity have been explored. A series of sixteen methyl piperazine incorporated phenyl benzamide and phenyl methanone derivatives have been synthesized and tested in a panel of three cancer cell lines (adenocarcinomic human alveolar basal epithelial cells (A-549), human colon carcinoma (HCT-116) and human pancreatic carcinoma (MIAPaCa-2)), using gefitinib as standard. Further, to study the probable mechanism, due to their structural similarity with EGFR inhibitors, docking interactions with EGFR active site were observed using Schrodinger suite.ResultThe results indicated that most of the compounds showed promising activity; out of which, compound A-11 was most active having cytotoxicity much better than that of gefitinib. It showed IC50 value of 5.71 µM against A-549 cell line, 4.26 µM against HCT-116 colon cancer line and 31.36 µM against MIAPaCa-2 cell line.ConclusionIt was found that these compounds fit well in the active site and may be exhibiting anticancer activity via EGFR inhibition.Graphical

Iodo-Annulations of N-Benzyl-propiolamides Leading To Azaspiro[5.5]undecatrienones or Benzo[c]azepinones

AbstractIodine-mediated oxidative annulations of N-benzyl-propiolamides are disclosed for the first time, providing either azaspiro[5.5]undecatrienones via dearomative ipso-annulation or benzo[c]azepinones through ortho-annulation. The selective construction of the aforementioned products is based on the ceric ammonium nitrate (CAN)-promoted divergent reactivity of the propiolamide, directed by the substituents on the phenyl ring of the N-benzyl group.