C60 Derivatives Research Articles

Synthesis, Biological Evaluation and Molecular Docking Studies of Benzimidazole Derivatives Substitutes as New Antimicrobial Agents

Benzimidazole derivatives have assumed an imperative moiety in the hypothetical improvement in heterocyclic science and furthermore utilized broadly in organic synthesis. The synthesis, structure and biological activities of benzimidazole derivatives have been focal point of research enthusiasm for the field of medication because of potential exercises displayed by them. Developments of more current lead atoms are utilized to improve pharmacological action and lessen drug toxicities. After extensive literature review it was thought worthwhile to synthesize some Benzimidazole derivatives and evaluate their antibacterial and antifungal activities. A series of new 2-(1<I>H</I>-benzimidazole-2-<i>yl</i>) phenyl)-2-(substituted benzylidene) hydrazine was designed for showing the above activity. The different hydrazine derivatives (4a-4i) were synthesized by using different substituted benzaldehyde compounds. The structures of synthesized compounds were characterized by IR, <sup>1</sup>H NMR, Mass spectral data and elemental analysis. Synthesized compounds were tested <i>in vitro</i> for different kinds of pharmacological activity of this class of medications including antibacterial and antifungal action. The compounds 4d and 4e found most active against <i>E.coli</i> and <i>P. aeurigenosa </i>and 4i found to be most active against <i>B.subtilis</i> and <i>S.aureus.</i> The derivative 4c shows good activity against <i>C.albicans </i>and <i>A.niger. </i>Molecular docking analysis was performed to investigate the binding affinity of the synthesized compounds with target proteins. By means of this research it is concluded that Benzimidazole derivatives are a potent compound compressing of different pharmacological activities and this has been proved by docking studies too. Further evaluation of their properties is required before they can be adopted for widespread use.

Chemical, antimicrobial, antioxidant, and molecular dynamic studies of spiro[chromane-3',2''-thiopyran]-4'-one 1''-oxide and spiro[chromane-3',2''-thiopyran]-4'-one 1'',1''-dioxide

Some of spiro[chromane-3',2''-thiopyran]-4'-ones were oxidized via m-chloroperbenzoic acid and/or hydrogen peroxide to afford the corresponding nine spiro[chromane-3',2''-thiopyran]-4'-one 1''-oxides and three spiro[chromane-3',2''-thiopyran]-4'-one 1'',1''-dioxides, which were confirmed by spectral data (IR, 1H NMR, 13C NMR, MS-ESI, and MS-EI). Whereas, the yield of oxidation using hydrogen peroxide is higher than that of oxidation using m-chloroperbenzoic acid. Moreover, Gram-negative bacteria (Escherichia coli ATCC 25922), and Gram-positive bacteria (Staphylococcus aureus ATCC 6538) were adopted to test the antimicrobial activity of 12 newly synthesized compounds (7a, 8a-c, 9a, 10a-c, 11a, 12a-c). The three sulfoxide derivatives 8b, 10b, and 10c showed antimicrobial activity. Also, antioxidant activity was evaluated for the newly synthesized compounds and shows that, all newly synthesized compounds (7a, 8a-c, 9a, 10a-c, 11a, 12a-c) have antioxidant activity. Molecular dynamic and system stability, Binding interaction mechanism based on binding free energy calculation, Identification of the critical residues responsible for ligands binding, Ligand–residue interaction network profiles, and In silico ADMET properties prediction were studied for the new compounds. The results of molecular dynamic studies were consistent with the in vitro antibacterial and antioxidant activity.

Experimental and theoretical investigations for novel 6-nitroquinoxaline-2,3‑dione derivatives: Synthesis, characterization, DFT calculations, ADME analysis, hirshfeld surface calculations, molecular docking studies, and antiproliferation evaluation

This work describes the synthesis of eight different 6-nitro-1,4-disubstituted-quinoxaline-2,3‑dione derivatives (4a-h). The starting material, 6-nitroquinoxaline-2,3‑dione 3 was prepared by reacting 4-nitro-o-phenylenediamine 1 with oxalic acid 2 at reflux in hydrochloric acid. Compound 3 was alkylated with various alkyl halides under solid-liquid phase transfer catalysis (PTC) to give the dialkyl quinoxalines (4a-h). The structures of all compounds obtained were elucidated based on spectroscopic measurements: 1H, 13C NMR, MS and UV spectroscopy and confirmed by single-crystal X-ray diffraction studies in the case of 4a, 4b, 4f, and 4h. The geometrical parameters and spectral data were also compared with those of a DFT geometry optimization and molecular orbital calculation at the B3LYP/6–311++G (d, p) level of theory. The closest contacts between the molecules of the four structures were investigated by analyzing their Hirshfeld surfaces and docking investigations in the protein EGFR (pdbid: 4HJO). Moreover, the experimental results are correlated to the calculated ones and showed great compatibility. Cell proliferation was used to measure the immunomodulatory activity of 4a-h compared to a control consisting only of normal cells cultured alone to determine their antiproliferative screening which concluded that the quinoxaline derivatives 4c, 4d, 4f and 4g showed immunomodulatory potential.

(Invited) 1. Chalcogen-Substituted PC61/71BX Derivatives in Perovskite Solar Cells

Taking into account the outstanding electronic and physical properties of fullerenes, novel functionalized fullerenes are synthesized, with adapted structures aimed at improving the efficiency and stability of inverted PSC architectures.By means of [2+1] cycloadditions, chalcogen-substituted fullerene C60 and C70 derivatives were successfully synthesized using tosylhydrazone derivatives containing thiophene, selenophene, and furan. These derivatives were based on the chemical structures of PC71BM and PC61BM, resulting in the preparation of PC71BX: T70, S70, and F70, and PC61BX: T60, S60 and F60. The chemical structure of the synthesized mono-adducts PC61/71BM was confirmed through 1H and 13C NMR spectroscopy, MALDI-TOF mass spectroscopy, UV-Vis spectroscopy, and cyclic voltammetry.Inverted PSCs were fabricated employing the synthesized chalcogen-substituted PC61/71BM as dopant-free ETLs. In the current presentation we will comment on the data obtained in this photovoltaic study and the explanation for the different behaviour of these PC61BX and PC71BX materials. Figure 1

Development of novel antibiotics derived from pyridazine: Synthesis, spectroscopic characterization, in vitro antimicrobial activity and molecular docking studies

In light of the increasing antibiotic resistance, it is crucial to discover new antimicrobial medications. Pyridazines are frequently investigated in research for the development of new chemical entities with enhanced therapeutic properties. Their structure allows for significant flexibility in the attachment of various functional groups, which is essential for drug discovery.Our work focuses on synthesizing new pyridazine derivatives (7a, 7b, 7c and 7d) through coupling reactions with various amino esters. The structures of these compounds have been analyzed using spectroscopic measurements including 1H, 13C NMR, IR, and mass spectroscopy. The compounds showed positive effects against two bacterial strains: Escherichia coli: ATCC25922 and Staphylococcus aureus: CIP543154. Molecular docking results of the protein 7AZ5 indicated significant affinities with these molecules through hydrogen bonds. Compounds 7a and 7d demonstrated the highest binding energies and the best antimicrobial activity, suggesting their potential as a model for creating novel and potent antimicrobial compounds.

Design and synthesis of novel Thiazolo[5,4-b]pyridine derivatives as potent and selective EGFR-TK inhibitors targeting resistance Mutations in non-small cell lung cancer

A novel series of substituted thiazolo[5,4-b]pyridine analogues were rationally designed and synthesized via a multi-step synthetic pathway, including Suzuki cross-coupling reaction. The anticancer activity of all forty-five synthesized derivatives was evaluated against HCC827, H1975, and A549 cancer cell lines utilizing the standard MTT assay. A significant number of the thiazolo[5,4-b]pyridine derivatives exhibited potent anticancer activity. Notably, compounds 10b, 10c, 10h, 10i, and 10k emerged as the most promising anticancer agents. The lead compound, N-(3-(6-(2-aminopyrimidin-5-yl)thiazolo[5,4-b]pyridin-2-yl)-2-methylphenyl)-2,5-difluorobenzenesulfonamide (10k), displayed remarkable potency with IC50 values of 0.010 μM, 0.08 μM, and 0.82 μM against the HCC827, NCI–H1975 and A-549 cancer cell lines, respectively, which were comparable to the clinically approved drug Osimertinib. Importantly, the potent derivatives 10b, 10c, 10h, 10i, and 10k exhibited selective cytotoxicity towards cancer cells and showing no toxicity against the normal BEAS-2B cell line at concentrations exceeding 35 μM. Mechanistic studies revealed that the active compound 10k acts as an EGFR-TK autophosphorylation inhibitor in HCC827 cells. Furthermore, apoptosis assays demonstrated that compound 10k induced substantial early apoptosis (31.9 %) and late apoptosis (8.8 %) in cancer cells, in contrast to the control condition exhibiting only 2.0 % early and 1.6 % late apoptosis. Molecular docking simulations of the synthesized compounds revealed that they formed essential hinge interactions and established hydrogen bonding with Cys797, indicating potential target engagement. These findings highlight the potential of the synthesized thiazolo [(Woodburn, 1999; Zigrossi et al., 2022) 5,45,4-b]pyridine derivatives as promising anticancer agents, warranting further investigation for the development of novel targeted therapies against non-small cell lung cancer.

Synthesis and Anti-Trypanosoma cruzi Activity of New Pyrazole-Thiadiazole Scaffolds.

Chagas disease, a silent but widespread disease that mainly affects a socioeconomically vulnerable population, lacks innovative safe drug therapy. The available drugs, benznidazole and nifurtimox, are more than fifty years old, have limited efficacy, and carry harmful side effects, highlighting the need for new therapeutics. This study presents two new series of pyrazole-thiadiazole compounds evaluated for trypanocidal activity using cellular models predictive of efficacy. Derivatives 1c (2,4-diCl) and 2k (4-NO2) were the most active against intracellular amastigotes. Derivative 1c also showed activity against trypomastigotes, with the detachment of the flagellum from the parasite body being a predominant effect at the ultrastructural level. Analogs have favorable physicochemical parameters and are predicted to be orally available. Drug efficacy was also evaluated in 3D cardiac microtissue, an important target tissue of Trypanosoma cruzi, with derivative 2k showing potent antiparasitic activity and a significant reduction in parasite load. Although 2k potentially reduced parasite load in the washout assay, it did not prevent parasite recrudescence. Drug combination analysis revealed an additive profile, which may lead to favorable clinical outcomes. Our data demonstrate the antiparasitic activity of pyrazole-thiadiazole derivatives and support the development of these compounds using new optimization strategies.

Novel hydroxy-tagged bis-dihydrazothiazole derivatives: Synthesis, antimicrobial capacity and formation of some metal chelates with iron, cobalt and zinc ions

Until today, microbialinfectionsepitomize a seriousuniversal health threat. Subsequently, developing a potential antimicrobialprototype remains an urgent, global necessity. Despite several reports discussing the biological utility of some bis-thiazoles, the use of bis-dihydrazothiazoles and their corresponding metal chelates as potent antimicrobials, is yet to be explored. The current report outlines an attempt to fill that void by representing a successful synthesis of a new class of bis-dihydrazothiazoles as well as three of their transition metal chelates and their use as potential antimicrobials. This report presents the design of some novel hydroxy-tagged bis-dihydrazothiazoles 6a-e and bis-dihydrazothiazolones 9a-evia the reaction of a bis-aldehyde thiosemicarbazone 3, as a common synthetic precursor, with two groups of hydrazonoyl halide derivatives 4a-e and 7a-e. The chelation affinity of these novel bis-dihydrazothiazoles to behave as neutral tridentate ligands coordinating to the metal ions; Fe(III), Co(II), or Zn(II) through azomethine-N, thiazole-S, and azo-N atoms to form metal complexes with a metal/ligand ratio of 2:1 was confirmed. In-vitro, antimicrobial screening of the novel hydroxy-tagged bis-dihydrazothiazole derivatives, as well as a selected group of their transition metal chelate complexes [M2L], was inspected, and the data weremeasured incomparisonto those of ketoconazole and gentamycin as antimicrobial reference standards. Most bis-dihydrazothiazoles 6a-e and bis-dihydrazothiazolones 9a-e showed decent to excellent antimicrobial activities against the screened microbes, but the chloro-substituted bis dihydrazothiazole derivatives 6c and 9c showed exceptional inhibition of Bacillus subtilis (20 mm), Escherichia coli (25 mm), and Candida albicans (19 mm), and Salmonella typhimurium (19 mm), respectively. Additionally, amongst the three synthesized metal complexes [M2L], only the zinc complex, [Zn2L] showed remarkable inhibition of both Staphylococcus aureus (21 mm) and Salmonella typhimurium (19 mm) compared to the reference standard Gentamycin, and was more potent than the free ligand, 6a itself (no activity and 11 mm respectively). Antimicrobial inspection was assessed by the agar well diffusion assay method against all bacterial and fungal strains. Magnetic moment, diffused reflectance, FT-IR, 1H NMR, molar conductivity, thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscope(SEM) were among the many techniques used to elucidate the structures of all novel hydroxy-tagged bis-heterocyclic ligands and their metal chelate complexes.

Synthesis of new pyrazine-pyrazole-thiazolidin-4-one and pyrazine-triazole-thiazolidin-4-one conjugates, molecular modelling and docking as antimicrobial agents

The ever-increasing incidence of microbial resistance provide a significant peril to the scientific community. Thus, the need for the discovery and development of new antimicrobial agents is becoming critical. An effective approach to address this challenging problem is to generate hybrid molecules by combining two or more pharmacophores covalently linked to a single-molecule platform. Antimicrobial hybrids have been proposed as promising solution to overcome drug resistance and/or presumably having a broader spectrum of activity. This guided us to synthesize a new series of eight final target pyrazine-pyrazole-thiazolidin-4-one and pyrazine-triazole-thiazolidin-4-one hybrids 7, 8a-c, 12, and 13a-c and investigate their biological activities. Characterization of the designed hybrids were performed using IR, 1H NMR, 13C NMR, and mass analyses. The DFT/B3LYP approach revealed that the synthesized hybrids had a non-planar configuration. The nitrobenzylidene derivatives 8c and 13c exhibited the highest polarizability and hyperpolarizability. We examined the antimicrobial activity, DNA gyrase inhibition, molecular docking, and Swiss ADME analysis of different pyrazine-pyrazole-thiazolidin-4-one and pyrazine-triazole-thiazolidin-4-one conjugates. These compounds are effective against a number of bacterial and fungal strains, suggesting possible treatments for certain infections. DNA gyrase inhibition experiments demonstrated that conjugate 13b was more effective than novobiocin. A molecular docking study sheds light on the binding affinities and interactions of these conjugates with target proteins, revealing strong and specific bindings for numerous conjugates. Swiss ADME studies examine important pharmacokinetic parameters and show issues with bioavailability and membrane permeability in the mouth because of variations in molecular weight, lipophilicity, and hydrogen bond interactions. Swiss ADME studies have studied the drug-like qualities of these conjugates, revealing their potential in antibacterial applications.

Synthesis, computational and UV–Vis absorption studies of novel sulfathiazole azo sulfonamides acting as potent antitubercular agents

In this work, we have reported the synthesis of unprecedented sulfonamide azo dyes 4(a-j) by the diazo-coupling reaction of sulfathiazole with various coupling components. Different spectroscopic techniques, like FT-IR, NMR (1H and 13C), and HRMS, were used to precisely assess the structures of the target molecules. The UV–Vis absorption study was conducted using variety of organic solvents. Quantum chemical calculations, geometrical optimization, and molecular electrostatic potential regions of all sulfathiazole azo colorants were explored using (DFT)/B3LYP method. The efficacy of the synthesized dyes in combatting M. tuberculosis was examined using the MABA assay; the derivatives 4c and 4h demonstrated promising activity with MIC of 1.56 µg/mL. Further, in silico molecular docking study was performed to elucidate the interactions with enoyl-ACP reductase. Target compounds were screened for their antimicrobial activity using the broth microdilution method against two gram-positive, two gram-negative bacterial strains, and a fungal strain. The cytotoxic potential of the active compounds was assessed using the MTT assay against the Vero cell line.

Synthesis of Cytotoxic Benzofurans and Ethers Derivatives of Paeonol.

Paeonol is a broadly studied natural product due to its many biological activities. Using a methodology previously employed by our research group, 11 derivatives of paeonol were synthesized (seven of them are unpublished compounds), including four ethers and seven benzofurans. Additionally, we determined the crystal structure of one of these ether derivatives (1 a) and of five benzofuran derivatives (2 a, 2 b, 2 c, 2 f and 2 g) by single crystal X-ray diffraction. To continue studying the cytotoxicity of this natural product and its derivatives, all compounds were tested against two cancer cell lines, HCT116 and MCF-7. Compounds 2 b, 2 e, and 2 g were considered active against the colorectal adenocarcinoma cells HCT116 (Growth inhibition >60 %). Compound 2 e showed an IC50 of 0.2 μM and was selected for further analysis, results reinforce its anticancer potential.

New 1,2,4-oxadiazole derivatives as potential multifunctional agents for the treatment of Alzheimer’s disease: design, synthesis, and biological evaluation

A series of new 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their anti-AD potential. The results revealed that eleven compounds (1b, 2a-c, 3b, 4a-c, and 5a-c) exhibited excellent inhibitory potential against AChE, with IC50 values ranging from 0.00098 to 0.07920 µM. Their potency was 1.55 to 125.47 times higher than that of donepezil (IC50 = 0.12297 µM). In contrast, the newly synthesized oxadiazole derivatives with IC50 values in the range of 16.64–70.82 µM exhibited less selectivity towards BuChE when compared to rivastigmine (IC50 = 5.88 µM). Moreover, oxadiazole derivative 2c (IC50 = 463.85 µM) was more potent antioxidant than quercetin (IC50 = 491.23 µM). Compounds 3b (IC50 = 536.83 µM) and 3c (IC50 = 582.44 µM) exhibited comparable antioxidant activity to that of quercetin. Oxadiazole derivatives 3b (IC50 = 140.02 µM) and 4c (IC50 = 117.43 µM) showed prominent MAO-B inhibitory potential. They were more potent than biperiden (IC50 = 237.59 µM). Compounds 1a, 1b, 3a, 3c, and 4b exhibited remarkable MAO-A inhibitory potential, with IC50 values ranging from 47.25 to 129.7 µM. Their potency was 1.1 to 3.03 times higher than that of methylene blue (IC50 = 143.6 µM). Most of the synthesized oxadiazole derivatives provided significant protection against induced HRBCs lysis, revealing the nontoxic effect of the synthesized compounds, thus making them safe drug candidates. The results unveiled oxadiazole derivatives 2b, 2c, 3b, 4a, 4c, and 5a as multitarget anti-AD agents. The high AChE inhibitory potential can be computationally explained by the synthesized oxadiazole derivatives’ significant interactions with the AChE active site. Compound 2b showed good physicochemical properties. All these data suggest that 2b could be considered as a promising candidate for future development.

Discovery and evolution of berberine analogues as anti-Helicobacter pylori agents with multi-target mechanisms

Thirty protoberberine derivatives, of which twenty five were new, were synthesized and evaluated for their anti-Helicobacter pylori (HP) activities, taking 2,3,10-trimethoxy-9-p-methylbenzylaminoprotopalmatine chloride 1 as the lead. Among them, berberine (BBR) derivative 7c displayed the highest potency against six tested metronidazole (MTZ)-resistant strains and two tested MTZ-susceptible strains with the MIC values of 0.4–1.6 μg/mL with favorable druglike profiles including low toxicity and high stabilities in plasma and artificial gastric fluid. Mechanistic study revealed that 7c might target HP urease with IC50 value of 0.27 μg/mL against Jack bean urease. Furthermore, 7c might change the permeability of the bacterial membrane and direct interact with HP DNA, which also contribute to its bactericidal activity. Therefore, BBR derivatives constituted a new family of anti-HP candidates, with the advantage of good safety profile and multi-target mechanisms, and are worthy for further investigation.

The Induction of G2/M Phase Cell Cycle Arrest and Apoptosis by the Chalcone Derivative 1C in Sensitive and Resistant Ovarian Cancer Cells Is Associated with ROS Generation.

Ovarian cancer ranks among the most severe forms of cancer affecting the female reproductive organs, posing a significant clinical challenge primarily due to the development of resistance to conventional therapies. This study investigated the effects of the chalcone derivative 1C on sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines. Our findings revealed that 1C suppressed cell viability, induced cell cycle arrest at the G2/M phase, and triggered apoptosis in both cell lines. These effects are closely associated with generating reactive oxygen species (ROS). Mechanistically, 1C induced DNA damage, modulated the activity of p21, PCNA, and phosphorylation of Rb and Bad proteins, as well as cleaved PARP. Moreover, it modulated Akt, Erk1/2, and NF-κB signaling pathways. Interestingly, we observed differential effects of 1C on Nrf2 levels between sensitive and resistant cells. While 1C increased Nrf2 levels in sensitive cells after 12 h and decreased them after 48 h, the opposite effect was observed in resistant cells. Notably, most of these effects were suppressed by the potent antioxidant N-acetylcysteine (NAC), underscoring the crucial role of ROS in 1C-induced antiproliferative activity. Moreover, we suggest that modulation of Nrf2 levels can, at least partially, contribute to the antiproliferative effect of chalcone 1C.

Metabolite responses of cucumber on copper toxicity in presence of fullerene C60 derivatives

Copper (Cu) toxicity in crops is a result of excessive release of Cu into environment. Little is known about mitigation of Cu toxicity through the application of carbon-based nanomaterials including water-soluble fullerene C60 derivatives. Two derivatives of fullerene were examined: polyhydroxylated C60 (fullerenol) and arginine C60 derivative. In order to study the response of Cu-stressed plants (Cucumis sativus L.) to these nanomaterials, metabolomics analysis by gas chromatography-mass spectrometry (GC-MS) was performed. Excess Cu (15 μM) caused substantial increase in xylem sap Cu, retarded dry biomass and leaf chlorosis of hydroponically grown cucumber. In Cu-stressed leaves, metabolomes was disturbed towards suppression metabolism of nitrogen (N) compounds and activation metabolism of hexoses. Also, upregulation of some metabolites involving in antioxidant defense system, such as ascorbic acid, tocopherol and ferulic acid, was occurred in Cu-stressed leaves. Hydroponically added fullerene adducts decreased the xylem sap Cu and alleviated Cu toxicity with effectiveness has been most pronounced for arginine C60 derivative. Metabolic responses of plants subjected to high Cu with fullerene derivatives were opposite to that observed under Cu alone. Fatty acids up-regulation (linolenic acid) and antioxidant molecules (tocopherol) down-regulation might indicate that arginine C60 adduct can alleviate Cu induced oxidative stress. Although fullerenol slightly improved cucumber growth, its effect on metabolic state of Cu-stressed plants was not statistically significant. We suggest that tested fullerene C60 adducts have a potential to prevent Cu toxicity in plants through a mechanism associated with their capability to restrict xylem transport of Cu from roots to shoot, and to maintain antioxidative properties of plants.

Synthesis, DFT, and in silico biological evaluation of chalcone bearing pyrazoline ring against Helicobacter pylori receptors

Peptic ulcer disease (PUD), often caused by Helicobacter pylori infection, is a prevalent gastrointestinal condition characterized by the erosion of the gastric or duodenal mucosal lining. H. pylori adheres to gastric epithelial cells, secreting toxins and disrupting the stomach's defenses. H. pylori relies on various receptors to establish infection, making these molecules attractive therapeutic targets. This study aimed to develop novel anti-ulcer compounds by combining benzothiazole, pyrazoline, and chalcone pharmacophores. A series of chalcone derivatives 4a-c were synthesized via Claisen-Schmidt condensation and characterized using spectroscopic techniques such as FT-IR, NMR and elemental analysis. The DFT calculations, using B3LYP method with 6-311G basis set, revealed the p-tolyl derivative 4b exhibited the highest thermal stability while the p-bromophenyl derivative 4c showed the lowest stability but highest chemical reactivity. The HOMO-LUMO energy gaps as well as the dipole moments decreased in the order: 4b > 4a >4c, reflecting a similar reactivity trend. Molecular docking showed ligands 4a-c bound effectively to the H. pylori urease enzyme, with docking scores from −5.3862 to −5.7367 kcal/mol with superior affinity over lansoprazole. Key interactions involved hydrogen bonds and hydrophobic pi-hydrogen bonds with distances ranging 3.46–4.34 Å with active site residues ASN666, SER714 and ASN810. The combined anti-inflammatory, antimicrobial, and H. pylori anti-adhesion properties make these novel chalcones promising PUD therapeutic candidates.

Non-covalent self-assembly of substituted phthalocyanine with C60, C70, and 9-phenylanthracene: Spectroscopic insights and DFT calculations

Self-assembly of non-covalent donor-acceptor systems based on (octakis-3,5-di-tert-butylphenoxy)phthalocyanine (H2Pc(3,5-tBuPhO)8) and С60, С70 or 9-phenylanthracene (PhAn) is observed and described using the UV–vis and steady-state/time-resolved fluorescence methods. The 1:1 stoichiometry of the H2Pc(3,5-tBuPhO)8 - С60/С70/PhAn supramolecule was established by Job's method. The fluorescence quenching of phthalocyanine in the mentioned systems in toluene, indicating close bonding between a donor and an acceptor, was observed. The bonding constants are 1.2 × 104 M−1, 2.4 × 104 M−1, and 3.9 × 102 M−1 for the C60, C70, and PhAn derivatives, respectively. Using time-resolved fluorescence measurements, the static mechanism of quenching was established. The H2Pc(3,5-tBuPhO)8 fluorescence lifetimes in the absence and presence of С60/С70/PhAn, the charge separation rate constant (kCS) and the charge-separated state quantum yield (ΦCS) of donor-acceptor systems were calculated. (С70)H2Pc(3,5-tBuPhO)8 displays the highest kCS and ΦCS in good agreement with its stability parameter. Quantum-chemical calculations of the molecular spatial/electronic structure and the HOMO/LUMO composition that were revealed by DFT and TD DFT methods point to the H2Pc(3,5-tBuPhO)8 → fullerenes redistribution of the electron density and to the opposite one in the PhAn complex.

Stereoselective Asymmetric Syntheses of Molecules with a 4,5-Dihydro-1H-[1,2,4]-Triazoline Core Possessing an Acetylated Carbohydrate Appendage: Crystal Structure, Spectroscopy, and Pharmacology.

A new series of chiral 4,5-dihydro-1H-[1,2,4]-triazoline molecules, featuring a β-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition reaction between various hydrazonyl chlorides and carbohydrate Schiff bases. The isolated enantiopure triazolines (8a-j) were identified through high-resolution mass spectrometry (HRMS) and vibrational spectroscopy. Subsequently, their solution structures were elucidated through NMR spectroscopic techniques. Single-crystal X-ray analysis of derivative 8b provided definitive evidence for the 3-D structure of this compound and revealed important intermolecular forces in the crystal lattice. Moreover, it confirmed the (S)-configuration at the newly generated stereo-center. Selected target compounds were investigated for anti-tumor activity in 60 cancer cell lines, with derivative 8c showing the highest potency, particularly against leukemia. Additionally, substituent-dependent anti-fungal and anti-bacterial behavior was observed.

Effect of substituents at the C3´, C3´N, C10 and C2-meta-benzoate positions of taxane derivatives on their activity against resistant cancer cells

We tested the effect of substituents at the (1) C3´, C3´N, (2) C10, and (3) C2-meta-benzoate positions of taxane derivatives on their activity against sensitive versus counterpart paclitaxel-resistant breast (MCF-7) and ovarian (SK-OV-3) cancer cells. We found that (1) non-aromatic groups at both C3´ and C3´N positions, when compared with phenyl groups at the same positions of a taxane derivative, significantly reduced the resistance of ABCB1 expressing MCF-7/PacR and SK-OV-3/PacR cancer cells. This is, at least in the case of the SB-T-1216 series, accompanied by an ineffective decrease of intracellular levels in MCF-7/PacR cells. The low binding affinity of SB-T-1216 in the ABCB1 binding cavity can elucidate these effects. (2) Cyclopropanecarbonyl group at the C10 position, when compared with the H atom, seems to increase the potency and capability of the derivative in overcoming paclitaxel resistance in both models. (3) Derivatives with fluorine and methyl substituents at the C2-meta-benzoate position were variously potent against sensitive and resistant cancer cells. All C2 derivatives were less capable of overcoming acquired resistance to paclitaxel in vitro than non-substituted analogs. Notably, fluorine derivatives SB-T-121205 and 121,206 were more potent against sensitive and resistant SK-OV-3 cells, and derivatives SB-T-121405 and 121,406 were more potent against sensitive and resistant MCF-7 cells. (4) The various structure-activity relationships of SB-T derivatives observed in two cell line models known to express ABCB1 favor their complex interaction not based solely on ABCB1.

New bioactive titanium(IV) derivatives with their DFT, molecular docking, DNA/BSA interaction, antioxidant and in-vitro investigations

A set of four new metallacyclic complexes titanium(IV) associated with Schiff bases (SBs) (1a- 1d) obtained by the specific reactions of β-diketones such as acetylacetone (acacH) and benzyl acetone (bzacH) and aminophenol derivatives while treating Ti(OPri)4 and these SBs individually in 1:2 stoichiometry under 8 h reflux condition in anhydrous benzene to afford as reddish powder (2a-2d). These products have been purified in repeated washings of dry n-hexane afterwards, subjected to characterization by suitable spectroscopic techniques (NMR, IR, UV–Vis and HRMS). These hexacoordinated complexes appeared as distorted octahedral geometry from computational data studies. The synthesized titanium(IV) complexes were screened for their antioxidant abilities where 2c and 2d exhibited remarkable activity as IC50 values. The DNA & BSA binding properties of the complexes (2a-2d) have also been investigated through electronic absorption and molecular docking analysis. The obtained results indicated clearly that the complexes got bound with DNA via groove binding mode according to the intrinsic binding constant values (Kb = 1.5 × 104 M−1 to 7.5 × 105 M−1). Derivative 2c was examined in-vitro on a panel of cancerous cell line − breast cancer and human colon cell lines MCF-7 to reflect IC50 results as 53.92 μg/mL and HT-29 33.43 μg/mL, respectively.