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We reported herein the synthesis, characterization of hybrid conjugates composed of phthalimide (Phth) and acridine-1,8-diones (Acr) for optical and medical applications. For the synthetic procedure, a three-step synthetic strategy has been utilized. The optical properties of the examined 1,8-acridinedione–phthalimide connected molecules (AcrPhth 1–5) have been examined utilizing various spectroscopic techniques, e.g., steady-state absorption and fluorescence, and time-correlated single photon counting. The steady-state absorption studies showed that AcrPhth 1–5 absorbs the light in the UV and visible region. The fluorescence studies of AcrPhth 1–5 exhibited significant fluorescence quenching compared to the acridinedione control compounds (Acr 1–5) suggesting the occurrence of electron-transfer reactions from the electron donating acridinedione moiety (Acr) to the electron accepting phthalimide moiety (Phth). The rate and efficiency of the electron-transfer reactions were determined from the fluorescence lifetime measurements indicating the fast electron-transfer processes of the covalently connected AcrPhth 1–5 conjugates. Computational studies supported the intramolecular electron-transfer reaction of AcrPhth conjugates using ab initio B3LYP/6-311G methods. In the optimized structures, the HOMO was found to be entirely located on the Acr entity, while the LUMO was found to be entirely on the Phth entity. Further, the synthesized compounds were tested as photosensitizers for generating the singlet oxygen species, which is a key factor in the photodynamic therapy (PDT) applications. The nanosecond laser flash measurements enable us to detect the triplet-excited states of examined Acr and AcrPhth conjugates, determining the triplet quantum yields, and direct detecting the singlet oxygen in an accurate way. From this observation, the singlet quantum yields were found to be in the range of 0.12–0.27 (for Acr 1–5) and 0.07–0.19 (for AcrPhth 1–5 conjugates). The molecular docking studies revealed that compound AcrPhth 2 exhibited high binding affinity with for key genes (p53, TOP2B, p38, and EGFR) suggesting its potential as a targeted anticancer therapy. [ABSTRACT FROM AUTHOR]

Candida species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six Nsubstituted phthalimides against three Candida species. Of the derivatives, Nbutylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 µg/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10-50 µg/ml) in both the fluconazole-resistant and fluconazole-sensitive Candida albicans and Candida parapsilosis.NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, and Vibrio parahaemolyticus, along with the polymicrobial biofilms of S. epidermidis and C. albicans. NBP markedly inhibited the hyphal formation and cell aggregation of C. albicans and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., ECE1, HWP1, and UME6, upon treatment.NBPalso exhibited mild toxicity at concentrations ranging from 2 to 20 µg/ml in a nematodemodel. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various Candida strains. [ABSTRACT FROM AUTHOR]

Two series of novel poly(ester-amide-imide)s (PEsAIs) with pendant phthalimide side group were synthesized by copolymerization of phthalimide-hydroquinone bis(trimellitate anhydride) (PI-TAHQ), p-phthaloyl chloride (TPC) and other fluorinated monomers using the two-step method. These PEsAIs had glass transition temperatures (Tgs) in the range of 228 °C-296°C and coefficients of thermal expansion (CTEs) of 18-55 ppm·K-1. These films had good mechanical properties with tensilemodulus of 3.7-5.7 GPa, tensile strengths of 92-153 MPa and elongations at break of 2.2%-8.3%. All films displayed good transparency with transmittances at 400 nm (T400nm) of 43%-79% and transmittances at 850 nm (T850nm) exceeding 89%, and these PEsAIs were amorphous. Especially, PEsAI-d-60 presented the best comprehensive performance with Tg of 296°C, low CTE of 18 ppm·K-1 and high transmittance (T400nm of 79%, T850nm of 91%), which exhibited the potential of this novel poly(ester-amide-imide) containing pendant phthalimide substituent in optical transparent materials. [ABSTRACT FROM AUTHOR]

Background: The synthesis and antibacterial efficacy of phthalimide Schiff bases derivatives (3a-f) derived from phthalic anhydride were investigated. The aim of this study was to assess the antibacterial activity of the synthesized Schiff bases against five different types of microbes in vitro. Methods: The Schiff bases were synthesized by reacting various aldehydes with the hydrazine of phthalimidobenzoic acid. The compounds were identified using FTIR and 1HNMR spectroscopy studies, and their antibacterial efficacy against four bacterial species ( Staphylococcus aureus, Streptococcus pyrogens, Escherichia coli, and Pseudomonas aeruginosa) and one fungal species ( Candida albicans) was assessed in vitro using a 100 µg/mL concentration of derivatives in dimethyl sulfoxide. Results: The antimicrobial activity of each compound towards the isolates was variable. Most of the compounds exhibited a slight inhibition rate towards Gram-positive and Gram-negative bacteria, particularly S. aureus, which was shown to be highly resistant to all derivatives used. However, there was moderate to high killing activity towards S. pyogenes. Conclusions: The synthesized phthalimide Schiff bases derivatives exhibited variable antibacterial activity against the tested microbes. The results suggest that further studies are required to optimize the efficacy of these compounds against harmful microorganisms.

The solubility of bisphenol A type phthalimide in different solvents at 273 ・ 15 〜353 ・ 15 K was measured by equilibrium method・ The results show that within a certain temperature range, the solubility increases with the increase of temperature・ Through the improved Apelblat equation, th equation and Wilson activity coefficient equation, the experimental data of the solubility was correlated・ And the correlation coefficients were not less than 0. 988 0,0. 977 1, and 0. 939 4, respectively・ The three models can correlate the solubility data of imide in solvent better・ Compared w让h the correlation results of the model, the improved Apelblat equation has the best correlation effect (ARD W6・ 18%, RSMD W2・ 39, and H2 M 0. 988 0), providing thermodynamics basis for the design of crystallization process. [ABSTRACT FROM AUTHOR]

The present investigation reports the efficient multistep synthesis of 1-(1,3-dioxoisoindolin-2-yl)-3-aryl urea analogs (7a–f) in good yields. All the 1-(1,3-dioxoisoindolin-2-yl)-3-aryl urea analogs (7a–f) were characterized by spectroscopic techniques. Five among the six compounds were tested against 56 cancer cell lines at 10 µM as per the standard protocol. 1-(4-Bromophenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7c) exhibited moderate but significant anticancer activity against EKVX, CAKI-1, UACC-62, MCF7, LOX IMVI, and ACHN with percentage growth inhibitions (PGIs) of 75.46, 78.52, 80.81, 83.48, 84.52, and 89.61, respectively. Compound 7c was found to exhibit better anticancer activity than thalidomide against non-small cell lung, CNS, melanoma, renal, prostate, and breast cancer cell lines. It was also found to exhibit superior anticancer activity against melanoma cancer compared to imatinib. Among the tested compounds, the 4-bromosubstitution (7c) on the phenyl ring demonstrated good anticancer activity. Docking scores ranging from −6.363 to −7.565 kcal/mol were observed in the docking studies against the molecular target EGFR. The ligand 7c displayed an efficient binding against the EGFR with a docking score of −7.558 kcal/mol and displayed an H-bond interaction with Lys745 and the carbonyl functional group. Compound 7c demonstrated a moderate inhibition of EGFR with an IC50 of 42.91 ± 0.80 nM, in comparison to erlotinib (IC50 = 26.85 ± 0.72 nM), the standard drug. The antioxidant potential was also calculated for the compounds (7a–f), which exhibited good to low activity. 1-(2-Methoxyphenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7f) and 1-(4-Methoxyphenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7d) demonstrated significant antioxidant activity with IC50 values of 15.99 ± 0.10 and 16.05 ± 0.15 µM, respectively. The 2- and 4-methoxysubstitutions on the N-phenyl ring showed good antioxidant activity among the series of compounds (7a–f). An in silico ADMET prediction studies showed the compounds' adherence to Lipinski's rule of five: they were free from toxicities, including mutagenicity, cytotoxicity, and immunotoxicity, but not for hepatotoxicity. The toxicity prediction demonstrated LD50 values between 1000 and 5000 mg/Kg, putting the compounds either in class IV or class V toxicity classes. Our findings might create opportunities for more advancements in cancer therapeutics. [ABSTRACT FROM AUTHOR]

Soluble polysilsesquioxane containing side-chain phthalimide groups (PSQ-PhI) was synthesized via a solvent- and catalyst-free hydrolytic polycondensation reaction using 2-[3-(triethoxysilyl)propyl]-1H-isoindole-1,3(2H)-dione. The composition and structure of polysilsesquioxane was confirmed via 1H, 13C, and 29Si NMR spectroscopy, Fourier transform infrared spectroscopy, gel permeation chromatography, thermogravimetric analysis, dynamic light scattering, X-ray diffraction analysis, and elemental analysis. The synthesized silsesquioxane showed a monomodal molecular weight distribution. The average molecular weight of polysilsesquioxane is 11,200 Da, and the polydispersity index is 1.10. 29Si NMR analysis showed a half-peak width w1/2 3.1 ppm at δ −68.3, which corresponds to the PhI(CH2)3SiO3/2 unit and indicates an ordered structure in the polymer, with some defects caused by the presence of uncondensed silanol groups. PSQ-PhI showed good thermal stability (Td5% decomposition at 345 °C). The polysilsesquioxane-based coating was transparent in the visible region. [ABSTRACT FROM AUTHOR]

A series of sulfenimide derivatives (1a-i) were investigated as inhibitors of human (hCA-I, hCA-II) and bovine (bCA) carbonic anhydrase enzymes. The compounds were synthesised by the reaction of substituted thiophenols with phthalimide by means of an effective, simple and eco-friendly method and the structures were confirmed by IR, 1H NMR, 13C NMR, MS and elemental analysis. All derivatives except for the methyl derivative (1b) exhibited effective inhibitory action at low micromolar concentrations on human isoforms, but only four derivatives (1e, 1f, 1h, 1i) inhibited the bovine enzyme. The bromo derivative (1f) was found to be strongest inhibitor of all three enzymes with KI values of 0.023, 0.044 and 20.57 µM for hCA-I, hCA-II and bCA, respectively. Results of our study will make valuable contributions to carbonic anhydrase inhibition studies for further investigations since inhibitors of this enzyme are important molecules for medicinal chemistry. [ABSTRACT FROM AUTHOR]

Phthalimide, a pharmacophore exhibiting diverse biological activities, holds a prominent position in medicinal chemistry. In recent decades, numerous derivatives of phthalimide have been synthesized and extensively studied for their therapeutic potential across a wide range of health conditions. This comprehensive review highlights the latest developments in medicinal chemistry, specifically focusing on phthalimide‐based compounds that have emerged within the last decade. These compounds showcase promising biological activities, including anti‐inflammatory, anti‐Alzheimer, antiepileptic, antischizophrenia, antiplatelet, anticancer, antibacterial, antifungal, antimycobacterial, antiparasitic, anthelmintic, antiviral, and antidiabetic properties. The physicochemical profiles of the phthalimide derivatives were carefully analyzed using the online platform pkCSM, revealing the remarkable versatility of this scaffold. Therefore, this review emphasizes the potential of phthalimide as a valuable scaffold for the development of novel therapeutic agents, providing avenues for the exploration and design of new compounds. [ABSTRACT FROM AUTHOR]

A positively charged nanofiltration (NF) membrane is known to have exceptional separation performance for bivalent cations in aqueous solutions. In this study, a new NF activity layer was created using interfacial polymerization (IP) on a polysulfone (PSF) ultrafiltration substrate membrane. The aqueous phase combines the two monomers of polyethyleneimine (PEI) and phthalimide, while successfully producing a highly efficient and accurate NF membrane. The conditions of the NF membrane were studied and further optimized. The aqueous phase crosslinking process enhances the polymer interaction, resulting in an excellent pure water flux of 7.09 L·m−2·h−1·bar−1 under a pressure of 0.4 MPa. Additionally, the NF membrane shows excellent selectivity toward inorganic salts, with a rejection order of MgCl2 > CaCl2 > MgSO4 > Na2SO4 > NaCl. Under optimal conditions, the membrane was able to reject up to 94.33% of 1,000 mg/L of MgCl2 solution at an ambient temperature. Further to assess the antifouling properties of the membrane with bovine serum albumin (BSA), the flux recovery ratio (FRR) was calculated to be 81.64% after 6 h of filtration. This paper presents an efficient and straightforward approach to customize a positively charged NF membrane. We achieve this by introducing phthalimide, which enhances the membrane's stability and rejection performance. HIGHLIGHTS A new positive-charge NF membrane was created for the separation of bivalent cations.; The composite NF membrane demonstrated excellent selectivity and permeability.; The composite NF membrane exhibited steady antifouling properties.;

A series of sulfenimide derivatives (1a-i) were investigated as inhibitors of human (hCA-I, hCA-II) and bovine (bCA) carbonic anhydrase enzymes. The compounds were synthesised by the reaction of substituted thiophenols with phthalimide by means of an effective, simple and eco-friendly method and the structures were confirmed by IR, 1H NMR, 13C NMR, MS and elemental analysis. All derivatives except for the methyl derivative (1b) exhibited effective inhibitory action at low micromolar concentrations on human isoforms, but only four derivatives (1e, 1f, 1h, 1i) inhibited the bovine enzyme. The bromo derivative (1f) was found to be strongest inhibitor of all three enzymes with KI values of 0.023, 0.044 and 20.57 µM for hCA-I, hCA-II and bCA, respectively. Results of our study will make valuable contributions to carbonic anhydrase inhibition studies for further investigations since inhibitors of this enzyme are important molecules for medicinal chemistry.

The major cause of hyperglycemia can generally be attributed to β-glucosidase as per its involvement in non-alcoholic fatty liver disease. This clinical condition leads to liver carcinoma (HepG2 cancer). The phthalimides and phthalamic acid classes possess inhibitory potential against glucosidase, forming the basis for designing new phthalimide and phthalamic acid analogs to test their ability as potent inhibitors of β-glucosidase. The study also covers in silico (molecular docking and MD simulations) and in vitro (β-glucosidase and HepG2 cancer cell line assays) analyses. The phthalimide and phthalamic acid derivatives were synthesized, followed by spectroscopic characterization. The mechanistic complexities associated with β-glucosidase inhibition were identified via the docking of the synthesized compounds inside the active site of the protein, and the results were analyzed in terms of the best binding energy and appropriate docking pose. The top-ranked compounds were subjected to extensive MD simulation studies to understand the mode of interaction of the synthesized compounds and binding energies, as well as the contribution of individual residues towards binding affinities. Lower RMSD/RMSF values were observed for 2c and 3c, respectively, in the active site, confirming more stabilized, ligand-bound complexes when compared to the free state. An anisotropic network model was used to unravel the role of loop fluctuation in the context of ligand binding and the dynamics that are distinct to the bound and free states, supported by a 3D surface plot. An in vitro study revealed that 1c (IC50 = 1.26 µM) is far better than standard acarbose (2.15 µM), confirming the potential of this compound against the target protein. Given the appreciable potential of the candidate compounds against β-glucosidase, the synthesized compounds were further tested for their cytotoxic activity against hepatic carcinoma on HepG2 cancer cell lines. The cytotoxicity profile of the synthesized compounds was performed against HepG2 cancer cell lines. The resultant IC50 value (0.048 µM) for 3c is better than the standard (thalidomide: IC50 0.053 µM). The results promise the hypothesis that the synthesized compounds might become potential drug candidates, given the fact that the β-glucosidase inhibition of 1c is 40% better than the standard, whereas compound 3c holds more anti-tumor activity (greater than 9%) against the HepG2 cell line than the known drug. [ABSTRACT FROM AUTHOR]

The results of investigation of the optical and electrochemical properties of substituted phthalimides linked to a cymantrenyl moiety by IR and NMR spectroscopy, UV-Vis spectroscopy, and cyclic voltammetry and also by DFT calculations are presented. It was shown that the optical, donor-acceptor, and redox properties of the organometallic phthalimides are affected by substituents in position 1 of the side chain of the cymantrene Cp and in position 4 of the phthalimide benzene ring. The reactions of dicarbonyl chelates with external ligands in the dark attest to hemilability of the Mn–O=C(imide) bond. [ABSTRACT FROM AUTHOR]

Thirteen new derivatives of the phthalimide‐1,2,3‐triazole‐N‐phenylacetamide hybrids were synthesized via simple chemical reactions. These hybrids were evaluated for their inhibitory potential against α‐glucosidase in vitro and in silico. Among these thirteen derivatives, seven compounds showed excellent inhibition against studied enzyme (IC50 values=1.30−31.7 μM) as compared to positive control acarbose (IC50 value=750.1 μM) and among them, compound with 2,4‐dichloro substituent on the phenyl ring of N‐phenylacetamide moiety was identified as the most potent inhibitor against α‐glucosidase. This compound was almost 577‐fold more active than acarbose. Kinetic study on the most potent compound demonstrated that this compound is a competitive α‐glucosidase inhibitor. To understand the interaction mode, stability, and flexibility of the most potent compounds, molecular docking and molecular dynamics studies were conducted. Furthermore, the drug‐likeness, pharmacokinetic, and toxicity properties of the title compounds were predicted by in silico studies. [ABSTRACT FROM AUTHOR]

The abietane diterpene (+)-ferruginol (1), like other natural and semisynthetic abietanes, is distinguished for its interesting pharmacological properties such as antimicrobial activity, including antiviral. In this study, selected C18-functionalized semisynthetic abietanes prepared from the commercially available (+)-dehydroabietylamine or methyl dehydroabietate were tested in vitro against human coronavirus 229E (HCoV-229E). As a result, a new ferruginol analogue caused a relevant reduction in virus titer as well as the inhibition of a cytopathic effect. A toxicity prediction based on in silico analysis was also performed as well as an estimation of bioavailability. This work demonstrates the antimicrobial and specifically antiviral activity of two tested compounds, making these molecules interesting for the development of new antivirals. [ABSTRACT FROM AUTHOR]

N‐[(4‐Fluorophenyl)sulfanyl]phthalimide (C14H8FNO2S, FP) was synthesized and characterized using X‐ray crystallography. It was then investigated via quantum chemical analysis using the density functional theory (DFT) approach, as well as spectrochemically using FT–IR and 1H and 13C NMR spectroscopy, and elemental analysis. The observed and stimulated spectra are in very good agreement for the DFT method. The in vitro antimicrobial activity of FP against three Gram‐positive bacteria, three Gram‐negative bacteria and two fungi were determined using the serial dilution method, and FP showed the highest antibacterial activity against E. coli, with a MIC of 128 µg ml−1. Druglikeness, ADME (absorption, distribution, metabolism and excretion) and toxicology studies were carried out to theoretically examine the drug properties of FP.N‐[(4‐Fluorophenyl)sulfanyl]phthalimide (FP) was investigated via quantum chemical analysis. Theoretical calculations (DFT) were used to predict the chemical and biological activities, and druglikeness results indicate that FP has a good physicochemical profile. These results can be used for future studies on drug development. Moreover, since FP is close to the nontoxicology limit, experimental in vitro studies could further support its potential as a drug candidate. [ABSTRACT FROM AUTHOR]

The advent of proteolysis-targeting chimaeras (PROTACs) mandates that new ligands for the recruitment of E3 ligases are discovered. The traditional immunomodulatory drugs (IMiDs) such as thalidomide and its analogues (all based on the phthalimide glutarimide core) bind to Cereblon, the substrate receptor of the CRL4ACRBN E3 ligase. We designed a thalidomide analogue in which the phthalimide moiety was replaced with benzotriazole, using an innovative synthesis strategy. Compared to thalidomide, the resulting “benzotriazolo thalidomide” has a similar binding mode, but improved properties, as revealed in crystallographic analyses, affinity assays and cell culture.

To design and develop novel antimicrobial agents, a series of phthalimide–triazine-based derivatives (6a–6e) were synthesized, characterized and evaluated for their potential antibacterial activities. The compounds were prepared through reaction of 6-phenyl-1,3,5-triazine-2,4-diamine with phthalimide moiety containing aliphatic amino acid. Structural analysis of the synthesized compounds was carried out by various characterization techniques such as FT-IR, 1H and 13C-NMR and mass spectroscopy. After the confirmation of the structure, the antibacterial screening of the synthesized compounds was performed against two strains of Gram-positive (Staphylococcus aureus, and Bacillus subtilis) and two strains of Gram-negative (Escherichia coli and Salmonella enteritidis) bacteria. The results of antimicrobial activity showed that compound 6d was the most active against all the tested strains of microorganisms with the MIC value 1.25 µg/µl. The synthesized compounds were docked into the binding sites of E. coli–DNA gyrase B and S. aureus–DNA gyrase complex to explore their theoretically binding mode and possible interactions of these ligands with these two targets. Docking study showed the importance of both hydrogen bonding and hydrophobic interactions as a key interaction with the targets. Based on the obtained results, the hybrid derivatives of triazine and phthalimide could be regarded as efficient candidates for further molecular developments of antimicrobial agents. [ABSTRACT FROM AUTHOR]

The design and synthesis of phthalimide derivatives are important goals for applications in fields such as pharmaceutical science and optoelectronics. In the present study, a facile and convenient synthetic pathway (no heat or acid/catalyst needed) is devised to produce phthalimides from a biomass‐derived furan by directly introducing an N‐carbamate group at the C‐2 position of the furan ring via thermal Curtius rearrangement. The electron‐donating N‐carbamate group increases the energy level of the highest occupied molecular orbital of the furan diene, resulting in a significant increase of the rate of the Diels–Alder reaction with maleimide compared to the conventional furfuryl furan. Interestingly, the Diels–Alder adduct smoothly undergoes aromatization (dehydration) to generate the phthalimide motif. It is shown that the biomass‐derived phthalimides can produce supramolecular gels and act as sensors of basic anions like F− and CN−. The novel synthetic pathway to phthalimide derivatives from a biomass‐derived furan can potentially be used to develop novel phthalimide motifs for a variety of applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Abietane diterpenoids are naturally occurring metabolites isolated from a large variety of plants, and many display antitumor properties. Tanshinones are abietane diterpenoids and were first isolated from Salvia miltiorrhiza "tanshen", a well-known traditional Chinese medicine, which has been used extensively for the treatment of coronary heart diseases as well as inflammatory diseases. Tanshinone IIA has shown the inhibition of tumor invasion and metastasis in vitro and in vivo, while abietane carnosol found in rosemary (Rosmarinus officinalis) has also exhibited in vitro and in vivo anticancer activities. However, there are few reports on the pharmacological properties of the structural analogues of both molecules. The aim of this study is to synthesize and to evaluate the antitumor activities of analogues of tanshinone and carnosol. In this study, we found that the analogues were able to inhibit the proliferation of four breast cancer cell lines. Our findings show that these readily available analogues can potentially serve as the foundation of an anti-breast cancer therapeutic agent development platform. The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC50 in the range 1.3–18.7 μM. This work demonstrates the antitumor activities of two tested compounds, making these molecules interesting for the development of new anticancer agents. [ABSTRACT FROM AUTHOR]

Isoindoles are highly reactive aromatic heterocycles that have a variety of important applications in areas such as medicine, analytical detection, and solar energy. Due to their highly reactive nature, isoindoles can be used to access their derivatives, which possess a diverse array of biological activities. However, their reactivity also makes isoindoles unstable and thus, difficult to prepare. Consequently, there has been a need for the development of novel methods that address some of the synthetic challenges and limitations, as well as reactions that utilize isoindoles to access potentially useful compounds. This review will give an overview of the novel reactions reported within the past decade (2012 to 2022) that involve 2 H - and 1 H -isoindoles and fused isoindoles as reactants, key intermediates, or products. This review is divided into two parts, with the first part focusing on the synthesis of isoindoles and the second part focusing on reactions of isoindoles. The scopes and limitations of the methods described therein will be discussed and the significance of their contributions to the literature will be highlighted. Similar reactions will also be compared. 1 Introduction 2 Synthesis of Isoindoles 2.1 Synthesis of 2 H -Isoindoles 2.2 Synthesis of 1 H -Isoindoles 3 Reactions of Isoindoles 3.1 Reactions of 2 H -Isoindoles 3.2 Reactions of 1 H -Isoindoles 4 Conclusions [ABSTRACT FROM AUTHOR]

In this study, thirteen phthalimide derivatives were designed and synthesized. All synthesized compounds were evaluated to determine their potential for inhibitory activities against females of the Caribbean fruit fly, Anastrepha suspensa (Loew) (Diptera: Tephritidae). These efforts led to the discovery of three compounds 4a, 4c, and 4d with potent insecticidal activity (LD50 range from 0.70 to 1.91 μg/fly). Among these compounds, 4a exhibited the highest inhibitory potency with 0.70 μg/fly. In addition, in silico models indicated that compound 4a is less toxic than phthalimide and other precursors. Therefore, our results suggest that 4a has strong potential as a candidate component for developing a novel environmentally friendly insecticide for control of pest fruit flies. [ABSTRACT FROM AUTHOR]

Herein, nine phthalimide-based thiazoles (4a–4i) were synthesized and investigated as new human neutrophil elastase (HNE) inhibitors using spectrofluorimetric and computational methods. The most active compounds containing 4-trifluoromethyl (4c), 4-naphthyl (4e) and 2,4,6-trichloro (4h) substituents in the phenyl ring exhibited high HNE inhibitory activity with IC50 values of 12.98–16.62 µM. Additionally, compound 4c exhibited mixed mechanism of action. Computational investigation provided a consistent picture of the ligand-receptor pattern of inter-actions, common for the whole considered group of compounds. Moreover, compounds 4b, 4c, 4d and 4f showed high antiproliferative activity against human cancer cells lines MV4-11, and A549 with IC50 values of 8.21 to 25.57 µM. Additionally, compound 4g showed high activity against MDA-MB-231 and UMUC-3 with IC50 values of 9.66 and 19.81 µM, respectively. Spectrophotometric analysis showed that the most active compound 4c demonstrated high stability under physiological conditions. [ABSTRACT FROM AUTHOR]

Soluble polysilsesquioxane containing side-chain phthalimide groups (PSQ-PhI) was synthesized via a solvent- and catalyst-free hydrolytic polycondensation reaction using 2-[3-(triethoxysilyl)propyl]-1H-isoindole-1,3(2H)-dione. The composition and structure of polysilsesquioxane was confirmed via 1H, 13C, and 29Si NMR spectroscopy, Fourier transform infrared spectroscopy, gel permeation chromatography, thermogravimetric analysis, dynamic light scattering, X-ray diffraction analysis, and elemental analysis. The synthesized silsesquioxane showed a monomodal molecular weight distribution. The average molecular weight of polysilsesquioxane is 11,200 Da, and the polydispersity index is 1.10. 29Si NMR analysis showed a half-peak width w1/2 3.1 ppm at δ −68.3, which corresponds to the PhI(CH2)3SiO3/2 unit and indicates an ordered structure in the polymer, with some defects caused by the presence of uncondensed silanol groups. PSQ-PhI showed good thermal stability (Td5% decomposition at 345 °C). The polysilsesquioxane-based coating was transparent in the visible region.

The present investigation reports the efficient multistep synthesis of 1-(1,3-dioxoisoindolin-2-yl)-3-aryl urea analogs (7a–f) in good yields. All the 1-(1,3-dioxoisoindolin-2-yl)-3-aryl urea analogs (7a–f) were characterized by spectroscopic techniques. Five among the six compounds were tested against 56 cancer cell lines at 10 µM as per the standard protocol. 1-(4-Bromophenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7c) exhibited moderate but significant anticancer activity against EKVX, CAKI-1, UACC-62, MCF7, LOX IMVI, and ACHN with percentage growth inhibitions (PGIs) of 75.46, 78.52, 80.81, 83.48, 84.52, and 89.61, respectively. Compound 7c was found to exhibit better anticancer activity than thalidomide against non-small cell lung, CNS, melanoma, renal, prostate, and breast cancer cell lines. It was also found to exhibit superior anticancer activity against melanoma cancer compared to imatinib. Among the tested compounds, the 4-bromosubstitution (7c) on the phenyl ring demonstrated good anticancer activity. Docking scores ranging from −6.363 to −7.565 kcal/mol were observed in the docking studies against the molecular target EGFR. The ligand 7c displayed an efficient binding against the EGFR with a docking score of −7.558 kcal/mol and displayed an H-bond interaction with Lys745 and the carbonyl functional group. Compound 7c demonstrated a moderate inhibition of EGFR with an IC50 of 42.91 ± 0.80 nM, in comparison to erlotinib (IC50 = 26.85 ± 0.72 nM), the standard drug. The antioxidant potential was also calculated for the compounds (7a–f), which exhibited good to low activity. 1-(2-Methoxyphenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7f) and 1-(4-Methoxyphenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7d) demonstrated significant antioxidant activity with IC50 values of 15.99 ± 0.10 and 16.05 ± 0.15 µM, respectively. The 2- and 4-methoxysubstitutions on the N-phenyl ring showed good antioxidant activity among the series of compounds (7a–f). An in silico ADMET prediction studies showed the compounds’ adherence to Lipinski’s rule of five: they were free from toxicities, including mutagenicity, cytotoxicity, and immunotoxicity, but not for hepatotoxicity. The toxicity prediction demonstrated LD50 values between 1000 and 5000 mg/Kg, putting the compounds either in class IV or class V toxicity classes. Our findings might create opportunities for more advancements in cancer therapeutics.

The advent of proteolysis-targeting chimaeras (PROTACs) mandates that new ligands for the recruitment of E3 ligases are discovered. The traditional immunomodulatory drugs (IMiDs) such as thalidomide and its analogues (all based on the phthalimide glutarimide core) bind to Cereblon, the substrate receptor of the CRL4ACRBN E3 ligase. We designed a thalidomide analogue in which the phthalimide moiety was replaced with benzotriazole, using an innovative synthesis strategy. Compared to thalidomide, the resulting "benzotriazolo thalidomide" has a similar binding mode, but improved properties, as revealed in crystallo-graphic analyses, affinity assays and cell culture. [ABSTRACT FROM AUTHOR]

In this paper, a novel and efficient method is reported for the synthesis of novel 2-substituted 3-thioxoisoindolin-1-one derivatives. The method is based on the solvent-free reaction of 2-carboxybenzaldehyde with aliphatic amines and sulfur at 100 °C. This reaction is intensely significant, especially in pharmacy applications, due to the facile synthesis of asymmetric thioxoisoindolin-1-one derivatives with phthalimide backbones. [ABSTRACT FROM AUTHOR]

The major cause of hyperglycemia can generally be attributed to β-glucosidase as per its involvement in non-alcoholic fatty liver disease. This clinical condition leads to liver carcinoma (HepG2 cancer). The phthalimides and phthalamic acid classes possess inhibitory potential against glucosidase, forming the basis for designing new phthalimide and phthalamic acid analogs to test their ability as potent inhibitors of β-glucosidase. The study also covers in silico (molecular docking and MD simulations) and in vitro (β-glucosidase and HepG2 cancer cell line assays) analyses. The phthalimide and phthalamic acid derivatives were synthesized, followed by spectroscopic characterization. The mechanistic complexities associated with β-glucosidase inhibition were identified via the docking of the synthesized compounds inside the active site of the protein, and the results were analyzed in terms of the best binding energy and appropriate docking pose. The top-ranked compounds were subjected to extensive MD simulation studies to understand the mode of interaction of the synthesized compounds and binding energies, as well as the contribution of individual residues towards binding affinities. Lower RMSD/RMSF values were observed for 2c and 3c, respectively, in the active site, confirming more stabilized, ligand-bound complexes when compared to the free state. An anisotropic network model was used to unravel the role of loop fluctuation in the context of ligand binding and the dynamics that are distinct to the bound and free states, supported by a 3D surface plot. An in vitro study revealed that 1c (IC50 = 1.26 µM) is far better than standard acarbose (2.15 µM), confirming the potential of this compound against the target protein. Given the appreciable potential of the candidate compounds against β-glucosidase, the synthesized compounds were further tested for their cytotoxic activity against hepatic carcinoma on HepG2 cancer cell lines. The cytotoxicity profile of the synthesized compounds was performed against HepG2 cancer cell lines. The resultant IC50 value (0.048 µM) for 3c is better than the standard (thalidomide: IC50 0.053 µM). The results promise the hypothesis that the synthesized compounds might become potential drug candidates, given the fact that the β-glucosidase inhibition of 1c is 40% better than the standard, whereas compound 3c holds more anti-tumor activity (greater than 9%) against the HepG2 cell line than the known drug.

A series of fluorescent phthalimidylhydrazone disperse dyes based on pyrrolinone esters were synthesized and characterized using Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance (1H-NMR) spectroscopy, and elemental analysis. The synthesized dyes were confirmed to be keto-hydrazone tautomers and were found to be mixtures of Z/E isomers, with the Z form being predominant, via 1H-NMR spectroscopy. Although the effect of N-alkylation in phthalimide on the absorption spectra and color properties of the dyed poly(ethylene terephthalate) (PET) was negligible, dyes that contained a longer N-alkyl substituent achieved higher color yields on the PET fabrics, owing to their increased hydrophobicity. The synthesized dyes exhibited a reasonably intense fluorescence in the solution state, with a quantum yield of 0.109–0.122, as well as in the dyed fabric. The phthalimidylhydrazone disperse dyes exhibited excellent color fastness after a mild alkaline treatment instead of the conventional reduction clearing, which causes environmental problems due to the high biochemical oxygen demand and alkalinity in dyehouse effluents. [ABSTRACT FROM AUTHOR]

Novel N-substituted phthalimide derivatives (4a–c) were synthesized using a three-step procedure in high yields. The inhibitory effects of these compounds against Electric eel acetylcholinesterase (eeAChE) and Equine serum butyrylcholinesterase (eqBChE) were examined in comparison with galantamine used as a standard drug. All compounds displayed quite good inhibition against both eeAChE and eqBChE. Compound 4b, carrying a 4-methyl piperidine moiety, showed the best activity against the both enzymes (IC50 = 0.052, Ki = 0.022 µM for eeAChE, and IC50 = 0.307, Ki = 0.112 µM for eqBChE) in noncompetitive inhibition type. In silico molecular docking studies detected that phthalimide ring, N-alkyl, and 4-methyl piperidine moieties of compound 4b were effective in the binding to the cholinesterase enzymes. The docking studies also showed that 4b has the best interaction energy value in agreement with our experimental data, and interacts with both catalytic active site (CAS) and peripheral anionic site (PAS) residues of eeAChE, while it interacts the CAS residues of homo sapiens BChE. In silico ADMET studies of all compounds suggested acceptable drug-likeness scores for these compounds. Consequently, the compounds, especially 4b, can be considered as new promising inhibitors for the cholinesterase enzymes. [ABSTRACT FROM AUTHOR]

Thieno[2,3-b]pyridine, a bicyclic heterocyclic, possesses various advantageous biological properties, including a cytotoxic effect. This study synthesized thieno pyridine scaffold derivatives with position 2 modifications. The reaction between 2-chloronicotinonitrile and methyl thioglycolate produced methyl amino thieno pyridine carboxylate 1. As a result of hydrazinolysis, methyl amino thieno pyridine carbohydrazide 2 was synthesized as a key compound for preparing final derivatives. The reaction of compound 2 with phthalic anhydride yielded thieno pyridine-phthalimide. The 1,3,4-oxadiazole scaffolds were synthesized in two steps. During the initial reaction of compound 2 with aroyle chloride derivatives, the corresponding intercessor was cyclized to oxadiazole in the presence of phosphoryl chloride. Compound 2 was subsequently cyclized in boiling glacial acetic acid to produce a pyridine-pyrazole derivative. MTT assay was utilized to assess the cytotoxic activity against two cell lines. Except for compound 6, the final compounds exhibited IC50 values <50 μM against both cell lines. Lipophilic compounds 4 and 5 exhibited significant cytotoxic effects compared to other compounds. [ABSTRACT FROM AUTHOR]

The title compounds, C23H25Br2NO2 (1) and C31H29BrN2O4 (2), crystallize in the space group P21/n with two (1-A and 1-B) and one molecules, respectively, in the asymmetric unit of the cell. The molecular conformation of these compounds is stabilized by intramolecular C—H...O hydrogen bonds and C—H...N or C—H...π interactions. The crystal structure of 1 features a relatively strong Br...O=C halogen bond, which is not observed in the case of 2. Both crystal structures are characterized by the presence of C—H...Br hydrogen bonds and numerous intermolecular C—H...O hydrogen-bonding interactions.

In this current study, a selected group of physicochemical descriptors extracted from the formalism of the density functional theory were used for modeling a series of phthalimide congeners with tested hypolipidemic activity once. Based on unsupervised pattern recognition of HCA and PCA followed by the PLS regressions, the final content may be considered trustful for predicting the biological activity due to the results of r2cal = 0.937, r2CV = 0.591 and r2test = 0.85. Moreover, the molecular modeling was performed through the docking protocol for predicting the ligand pose on the HMG-CoA reductase. The protocols of the AutoDock Tools and AutoDock Vina were used for determining the interaction scores (ΔG) and inhibition constants (Ki). Among all congeners studied, the docking results pointed out a potential compound. By taking into account the widely known top selling drugs, and just as is well-known that atorvastatin is one of them due its capability to lower the cholesterol levels, the structure of this drug was subjected to a docking study in order to guide us to a better understanding of the results available here. DOI: http://dx.doi.org/10.17807/orbital.v13i3.1493

The abietane diterpene (+)-ferruginol (1), like other natural and semisynthetic abietanes, is distinguished for its interesting pharmacological properties such as antimicrobial activity, including antiviral. In this study, selected C18-functionalized semisynthetic abietanes prepared from the commercially available (+)-dehydroabietylamine or methyl dehydroabietate were tested in vitro against human coronavirus 229E (HCoV-229E). As a result, a new ferruginol analogue caused a relevant reduction in virus titer as well as the inhibition of a cytopathic effect. A toxicity prediction based on in silico analysis was also performed as well as an estimation of bioavailability. This work demonstrates the antimicrobial and specifically antiviral activity of two tested compounds, making these molecules interesting for the development of new antivirals.

Tetrachlorinated phthalimide analogues bearing a boron-pinacolate ester group were synthesised via two synthetic routes and evaluated in their glycosidase modulating and anticancer properties, with a view to use them in boron neutron capture therapy (BNCT), a promising radiation type for cancer, as this therapy does little damage to biological tissue. An unexpected decarbonylation/decarboxylation to five 2,3,4,5-tetrachlorobenzamides was observed and confirmed by X-ray crystallography studies, thus, giving access to a family of borylated 2,3,4,5-tetrachlorobenzamides. Biological evaluation showed the benzamide drugs to possess good to weak potencies (74.7–870 μM) in the inhibition of glycosidases, and to have good to moderate selectivity in the inhibition of a panel of 18 glycosidases. Furthermore, in the inhibition of selected glycosidases, there is a core subset of three animal glycosidases, which is always inhibited (rat intestinal maltase α-glucosidase, bovine liver β-glucosidase and β-galactosidase). This could indicate the involvement of the boron atom in the binding. These glycosidases are targeted for the management of diabetes, viral infections (via a broad-spectrum approach) and lysosomal storage disorders. Assays against cancer cell lines revealed potency in growth inhibition for three molecules, and selectivity for one of these molecules, with the growth of the normal cell line MCF10A not being affected by this compound. One of these molecules showed both potency and selectivity; thus, it is a candidate for further study in this area. This paper provides numerous novel aspects, including expedited access to borylated 2,3,4,5-tetrachlorophthalimides and to 2,3,4,5-tetrachlorobenzamides. The latter constitutes a novel family of glycosidase modulating drugs. Furthermore, a greener synthetic access to such structures is described. [ABSTRACT FROM AUTHOR]

In these studies, we investigated the antioxidant activity of three ruthenium cyclopentadienyl complexes bearing different imidato ligands: (η5-cyclopentadienyl)Ru(CO)2-N-methoxysuccinimidato (1), (η5-cyclopentadienyl)Ru(CO)2-N-ethoxysuccinimidato (2), and (η5-cyclopentadienyl)Ru(CO)2-N-phthalimidato (3). We studied the effects of ruthenium complexes 1–3 at a low concentration of 50 µM on the viability and the cell cycle of peripheral blood mononuclear cells (PBMCs) and HL-60 leukemic cells exposed to oxidative stress induced by hydrogen peroxide (H2O2). Moreover, we examined the influence of these complexes on DNA oxidative damage, the level of reactive oxygen species (ROS), and superoxide dismutase (SOD) activity. We have observed that ruthenium complexes 1–3 increase the viability of both normal and cancer cells decreased by H2O2 and also alter the HL-60 cell cycle arrested by H2O2 in the sub-G1 phase. In addition, we have shown that ruthenium complexes reduce the levels of ROS and oxidative DNA damage in both cell types. They also restore SOD activity reduced by H2O2. Our results indicate that ruthenium complexes 1–3 bearing succinimidato and phthalimidato ligands have antioxidant activity without cytotoxic effect at low concentrations. For this reason, the ruthenium complexes studied by us should be considered interesting molecules with clinical potential that require further detailed research. [ABSTRACT FROM AUTHOR]

In this work, a novel series of phthalimide-4,5-dihydrothiazole-amide derivatives 5a–f have been synthesized and evaluated for their anti-epileptic activities against pentylenetetrazole (PTZ)-induced seizure in mice. Among the synthesized compounds, the most potent was 4-chloro derivative 5b with zero mortality in PTZ test. Molecular docking was performed to investigate the modes of interactions between GABAA receptor and synthetized compounds. Docking results were in good agreement with observed experimental data and indicate that among six new derivatives, compound 5b with highest effective anticonvulsant properties, had lowest binding energy. This compound also exhibited better anti-epileptic activity and lower binding energy for connect to GABAA receptor in comparison to thalidomide as standard anti-epileptic agent. [ABSTRACT FROM AUTHOR]

Objective(s): Cancer is the second important reason for death worldwide. In spite of advances in cancer treatment, however, survival of patients stays weak. Therefore, there is a critical need for advancement of new anticancer drugs. Regarding the hopeful biological activity of phthalimide derivatives, in this study, synthesis, cytotoxicity, and pro‐apoptosis activity of eleven derivatives of thiazole bearing phthalimide structure were evaluated.Materials and Methods: First, target derivatives were synthesized. All synthesized compounds were characterized by spectroscopic methods. Cytotoxicity and pro‐apoptosis activity of the synthesized compounds were evaluated in MDA-MB-468, PC-12, and MCF-7 cancer cell lines by MTT assay, caspase-3 activity, and TUNEL assay. Finally, expression of BAX, BCL-2, and FAS (as markers of apoptosis) was assessed by the RT-PCR procedure.Results: Among the eleven compounds, 5b (IC50 = 0.2±0.01 µM) was found to be the most potent derivative against MCF-7 cells. Also, Compound 5k and 5g showed strong cytotoxic activity against MDA-MB-468 and PC-12 cells with IC50 value of 0.6±0.04 µM and 0.43±0.06 µM, respectively. DNA fragmentation and activity of caspase-3 data suggest that cytotoxic activity of the compounds on cancer cells might be related to apoptosis. Also, RT-PCR of apoptosis markers indicated that these compounds induce apoptosis through the intrinsic pathway.Conclusion: Our findings suggest that para chloro derivative (5c) may be a promising agent for treatment of cancer cells by the targeted intrinsic pathway of apoptosis and could be used as a drug candidate for in vivo assessment in the treatment of cancer.

• Structural determination of three new phtalimidoethane sulfonamide compounds. • Detailed theoretical analysis including electronic and optical studies. • The investigation of inhibition properties of the compounds against Alzheimer's disease. • Supporting theoretical studies to gain insight into biological activity. The three N -substituted-2-phtalimidoethanesulfonamide derivatives, 2-(1,3-dioxoisoindolin-2- yl)- N -(2-isopropylphenyl)ethane-1-sulfonamide (I), N -(2,6-dimethylphenyl)-2-(1,3-dioxoiso indolin-2-yl)ethane-1-sulfonamide (II) and 2-(2-(morpholinosulfonyl)ethyl) isoindoline-1,3‑dione (III), were analyzed using a combined approach including single-crystal X-ray diffraction (SC-XRD), theoretical calculations with Density Functional Theory (DFT), and molecular docking studies. Phthalimide and sulfonamide compounds have recently attracted attention for their inhibitory properties against AChE and BChE enzymes. In this study, molecular and crystal structures of compounds have been confirmed by the SC-XRD technique. Optimized molecular geometries and vibrational modes have been examined and compared to experimental results. Frontier molecular orbital (HOMO-LUMO) energies, molecular electrostatic potential (MEP), natural bond orbital (NBO) analysis, and non-linear optical (NLO) properties have been investigated by DFT/B3LYP/6–311G++(d,p) method. The reduced density gradient (RDG) analysis has been performed to analyze the non-covalent interactions. The Hirshfeld surfaces and 2D fingerprint analyses have been used to determine the intermolecular interactions of compounds. Moreover, in silico docking studies are performed to investigate the interactions between N -substituted-2-phtalimidoethane sulfonamide derivatives and AChE and BChE enzymes. [Display omitted] [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CP) is a mutagen that is used in cancer chemotherapy, due to its genotoxicity and as an immunosuppressive agent. Thalidomide (TH) is another cancer chemotherapeutic drug. In this study, the cytogenotoxicity and hypoxia modulatory activities of two phthalimide analogs of TH have been evaluated with/without CP. Both analogs have increased CP-stimulated chromosomal aberrations than those induced by TH, including gaps, breaks/fragments, deletions, multiple aberrations, and tetraploidy. The analogs have elevated the cytotoxic effect of CP by inhibiting the mitotic activity, in which analog 2 showed higher mitosis inhibition. CP has induced binucleated and polynucleated bone marrow cells (BMCs), while micronuclei (MN) are absent. TH and analogs have elevated the CP-stimulated binucleated BMCs, while only analogs have increased the CP-induced polynucleated BMCs and inhibited the mononucleated BMCs. MN-BMCs were shown together with mononucleated, binucleated, and polynucleated cells in the CP group. Both analogs have elevated mononucleated and polynucleated MN-BMCs, whereas in presence of CP, TH and analogs have enhanced mononucleated and binucleated MN-BMCs. The analogs significantly induce DNA fragmentation in a comet assay, where analog 1 is the strongest inducer. The treatment of mice with CP has resulted in a high hypoxia status as indicated by high pimonidazole adducts and high HIF-1α and HIF-2α concentrations in lymphocytes. Analogs/CP-treated mice showed low pimonidazole adducts. Both analogs have inhibited HIF-1α concentration but not HIF-2α. Taken together, the study findings suggest that both analogs have a higher potential to induce CP-genotoxicity than TH and that both analogs inhibit CP-hypoxia via the HIF-1α-dependent mechanism, in which analog 1 is a more potent anti-hypoxic agent than analog 2. Analog 1 is suggested as an adjacent CP-complementary agent to induce CP-genotoxicity and to inhibit CP-associated hypoxia.

Background and purpose: In the last few decades, nitrogen-rich heterocyclic compounds such as 1, 3, 4-thiadiazoles, 1, 2, 4-triazoles and 1, 3, 4-oxadiazoles have received considerable attention because of their notable biological properties, especially cytotoxic effects. The small molecules of mentioned azole derivatives revealed very intensive antitumor activity. In addition, phthalimide-thiadiazole and naphthalimide-triazole hybrid derivatives have shown remarkable cytotoxic effects. According to these observations, some of the hybrid derivatives containing the phthalimide-five-membered azoles were prepared in three steps in this research. Experimental approach: The thiol group of azoles was treated with ethyl chloroacetate which was followed by a reaction with hydrazine hydrate to provide acid hydrazide derivatives. Subsequently, the corresponding acid hydrazides were utilized to prepare the final derivatives through the reaction with phthalic anhydride. Cytotoxic activity of final compounds was evaluated against MCF-7 and HeLa cell lines using MTT assay. Findings/Results: Compound 3d containing two phthalimide moieties in its structure showed a significant improvement in cytotoxic activity with an IC50 value of 29 μM against HeLa cell line. Compounds 3a-3c showed less cytotoxic effects against both cell lines. Conclusion and implications: The combination of the thiadiazole nucleus with two phthalimide structures increased the cytotoxic activity against the HeLa cell line. This increase in cytotoxic activity is probably due to its being more lipophilic characteristic and interaction of this derivative with the biological targets of two directions.

Aromatic polyimides (PIs) exhibit excellent mechanical and thermal properties due to the charge transfer (CT) interactions. The introduction of benzimidazole with hydrogen interactions is a notably effective strategy for yielding exceptional superheat resistance and high thermal dimensional stability of PIs. Decoupling the stacking behavior under CT interactions and hydrogen interactions is crucial for elucidating the behavior of PIs macromolecules. Herein, the packing structure of PIs guided by hydrogen interactions was visualized using three plausible model compounds and theoretical simulations. The phthalimide fragment exhibited a preference for anti-parallel offset stack π-π stacking, while the phenylbenzimidazole fragment formed a shoulder-to-shoulder arrangement, resulting in the adoption of a Mixed Layer Packing (MPL) conformation, which is not the common Preferred Layer Packing (PLP) conformation. The CT interactions of phthalimide served as the primary stacking driving force, rather than the hydrogen interaction of benzimidazole. The intrinsic nature of packing behavior was that the minima and maxima parts of the electron density deviated from the midperpendicular of benzene and succinimide, where the LOL-π map, ESP map and SAPT calculations provided insights into the microscopic electronic structure. Finally, experimental PI fibers was prepared and their XRD pattern further confirmed the presence of an anti-parallel offset π-π stack conformation. [Display omitted] • Decoupling the stacking behavior of PIs under CT interactions and hydrogen interactions. • Three crystal structures are reported firstly and the filled structures of benzimidazole-containing PIs are investigated by theoretical calculations. • The phthalimide fragment exhibited anti-parallel offset stack π-π stacking, while the phenylbenzimidazole fragment formed shoulder-to-shoulder arrangement. [ABSTRACT FROM AUTHOR]

A series of triterpenoid pyrones was synthesized and subsequently modified to introduce phthalimide or phthalate moieties into the triterpenoid skeleton. These compounds underwent in vitro cytotoxicity screening, revealing that a subset of six compounds exhibited potent activity, with IC 50 values in the low micromolar range. Further biological evaluations, including Annexin V and propidium iodide staining experiment revealed, that all compounds induce selective apoptosis in cancer cells. Measurements of mitochondrial potential, cell cycle analysis, and the expression of pro- and anti-apoptotic proteins confirmed, that apoptosis was mediated via the mitochondrial pathway. These findings were further supported by cell cycle modulation and DNA/RNA synthesis studies, which indicated a significant increase in cell accumulation in the G0/G1 phase and a marked reduction in S-phase cells, alongside a substantial inhibition of DNA synthesis. The activation of caspase-3 and the cleavage of PARP, coupled with a decrease in the expression of Bcl-2 and Bcl-XL proteins, underscored the induction of apoptosis through the mitochondrial pathway. Given their high activity and pronounced effect on mitochondria function, trifluoromethyl pyrones 1f and 2f , and dihydrophthalimide 2h have been selected for further development. [Display omitted] • A set of novel triterpenoid pyrones, phthalimides and phthalates was synthesized. • Six compounds with high in vitro cytotoxicity in CCRF-CEM cells was identified. • All compounds induce apoptosis via the mitochondrial intrinsic pathway. • Pyrones 1f , 2f , and dihydrophthalimide 2h were selected for further development. [ABSTRACT FROM AUTHOR]

The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC50 in the range 1.3–18.7 μM. This work demonstrates the antitumor activities of two tested compounds, making these molecules interesting for the development of new anticancer agents.

A novel HPLC method for simultaneous detecting bulky imides and their hydrolyzed products by D-hydantoinase was established. Phthalimide (PI) and 2,3-pyridinedicarboximide (PDI) can be regiospecifically hydrolyzed by engineered strain pET3a-hyd/Escherichia coli BL21(DE3) expressed D-hydantoinase into phthalamic acid (PA) and 3-carbamoyl-α-picolinic acid (α-3CP). The processes were analyzed by HPLC with H2O-acetonitrile as mobile phase containing 0.1% (v/v) trifluoroacetic acid at 254 nm (PDI, α‑3CP and β-2CP) and 220 nm (PI and PA) detector wavelength, respectively. The specific activities of the engineered strain account for 0.15 U/(mL × 10 OD600) to PI and 0.61 U/(mL × 10 OD600) to PDI. [ABSTRACT FROM AUTHOR]

An efficient and convenient three-component reaction of dialkyl acetylene dicarboxylates with trialkyl(aryl) phosphites in the presence of maleimide or phthalimide provides a straightforward approach to the synthesis of stable dialkyl(aryl) phosphoryl succinates in excellent yields. While the reactions were carried out in the presence of triphenylphosphine, stabilized phosphoranes, obtained from three component reaction, undergo a smooth intramolecular Wittig reaction in boiling toluene to produce functionalized 2H-pyrrol-2-ones in good yields. [ABSTRACT FROM AUTHOR]

A series of amino derivatives of 5-arylisoxazoles and 4,5-dichloroisothiazole with primary and secondary amino groups was synthesized. 3-Aminomethyl-5-arylisoxazol-3-ylmethanamines were obtained on the basis of 5-aryl-3-(chloromethyl)isoxazoles using the Gabriel phthalimide method. 5-Arylisoxazol-3-yl- and 4,5-dichloroisothiazol-3-ylallylamines were synthesized in two ways: reduction of azomethines obtained by condensation of 5-arylisoxazolyl- and 4,5-dichloroisothiazolyl-3-carbaldehydes with allylamine, and by nucleophilic substitution of the chlorine atom in 3-chloromethyl derivatives of the corresponding azoles by reaction with allylamine. Amides and sulfonamides of azolylallylamines were synthesized. Some of the compounds obtained showed antibacterial and fungicidal activity. [ABSTRACT FROM AUTHOR]