Conventional and microwave-assisted synthesis of new indole-tethered benzimidazole-based 1,2,3-triazoles and evaluation of their antimycobacterial,antioxidant and antimicrobial activities

A new series of triheterocycles containing indole–benzimidazole-based 1,2,3-triazole hybrids have been synthesized in good yields via a microwave-assisted click reaction. All the compounds were characterized by IR, \(^{1}\hbox {H}\) NMR, \(^{13}\hbox {C}\) NMR and mass spectroscopy and were evaluated for their in vitro antitubercular activity against the Mycobacterium tuberculosis H37Rv strain. Compounds 4b, 4h and 4i displayed highly potent antitubercular activity with MIC 3.125–6.25 \(\upmu \hbox {g}/\hbox {mL}\). The antioxidant potential was evaluated using 2,2-diphenyl-1-picryl hydrazine and \(\hbox {H}_{2}\hbox {O}_{2}\) radical scavenging activity, and compounds 4e,4f and 4g showed excellent radical scavenging activity with \(\hbox {IC}_{50}\) values in the range of 08.50–10.05 \(\upmu \hbox {g}/\hbox {mL}\). Furthermore, the compounds were evaluated for antimicrobial activity against numerous bacterial and fungal strains, and compounds 4b, 4c and 4h were found to be the most promising potential antimicrobial molecules with MIC 3.125–6.25 \(\upmu \hbox {g}/\hbox {mL}\).     

Design,synthesis, in silico and biological evaluation of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazine carboxamides

A series of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazinecarboxamide derivatives has been successfully designed and synthesized to evaluate their potential as carbonic anhydrase (CA) inhibitors. The inhibitory potential of synthesized compounds against human CAI and CAII was evaluated. Compounds 3a–n exhibited \(\hbox {IC}_{50}\) values between \(1.89{-}415.1\,\upmu \hbox {M}\) against CAI and \(0.62{-}66.9\,\upmu \hbox {M}\) against CAII. Compound 3g was the most active inhibitor, with an \(\hbox {IC}_{50}\) value of \(0.62\,\upmu \hbox {M}\) against CAII. Molecular docking studies of compound 3g with CAII showed this compound fits nicely in the active site of CAII and it interacts with the zinc ion (\(\hbox {Zn}^{2+}\)) along with three histidine residues in the active site. Molecular dynamics simulation studies of compound 3g complexed with CAII also showed essential interactions which were maintained up to 40 ns of simulation. In vivo sub-acute toxicity study using 3g (300 mg/kg) was found non-toxic in adult Wistar rats.     

Synthesis,in vitro $$\alpha $$-glucosidase inhibitory activity,and in silico study of ( E)-thiosemicarbazones and ( E)-2-(2-(arylmethylene)hydrazinyl)-4-arylthiazole derivatives

This study is focused on the identification of thiazole-based inhibitors for the \(\alpha \)-glucosidase enzyme. For that purpose, (E)-2-(2-(arylmethylene)hydrazinyl)-4-arylthiazole derivatives were synthesized in two steps and characterized by various spectroscopic techniques. All derivatives and intermediates were evaluated for their in vitro \(\alpha \)-glucosidase inhibitory activity. Thiosemicarbazones 20 and 35, and cyclized thiazole derivatives 2, 5–11, 13, 15, 21–24, 27–31, and 36–37 showed significant inhibitory potential in the range of \(\hbox {IC}_{50}=6.2\pm 0.19\)–\(43.6\pm 0.23~\upmu \hbox {M}\) as compared to standard acarbose (\(\hbox {IC}_{50}=37.7\pm 0.19~\upmu \hbox {M}\)). A molecular modeling study was carried out to understand the binding interactions of compounds with the active site of enzyme.     

Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides

The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer’s disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase \((h\hbox {BChE})\) (\(\hbox {IC}_{50}\) values \(0.80\,\pm 0.05\) and \(0.25\,\pm 0.02\,{\upmu }\hbox {M}\), respectively).     

Design and one-pot synthesis of 2-thiazolylhydrazone derivatives as influenza neuraminidase inhibitors

Two series of novel 2-thiazolylhydrazone derivatives were designed and synthesized via one-pot reaction of benzaldehyde derivatives, \(\alpha \)-haloketones and thiosemicarbazide. The structures of compounds 1 and 2 were characterized by \(^{1}\hbox {H}\) NMR and \(^{13}\hbox {C}\) NMR, and compound 1g was further confirmed by X-ray crystallography. All of the target compounds were evaluated for their NA inhibitory activity against influenza viral neuraminidase (H1N1) in vitro, and the results showed that many compounds exhibited moderate to strong inhibitory activities against influenza viral neuraminidase (H1N1). Among them, compounds 1p, 1q and 2c showed the most potent inhibitory activities with \(\hbox {IC}_{50}\) values ranging from 10.50 to \(13.75\, \upmu \hbox {g}/\hbox {mL}\). Our structure–activity relationship analysis indicated that 2-thiazolylhydrazone is an effective scaffold for NA inhibitors and that introducing an ethoxycarbonyl group to the 5-position of thiazole ring could enhance inhibitory potency. Molecular docking was performed on the most active compounds 1p and 2c to provide more insight into their mechanism of interaction.     

Synthesis,characterization and molecular docking studies of thiouracil derivatives as potent thymidylate synthase inhibitors and potential anticancer agents

Thymidylate synthase (TS), one of folate-dependent enzymes, is a key and well-recognized target for anticancer agents. In this study, a series of 6-aryl-5-cyano thiouracil derivatives were designed and synthesized in accordance with essential pharmacophoric features of known TS inhibitors. Nineteen compounds were screened in vitro for their anti-proliferative activities toward HePG-2, MCF-7, HCT-116, and PC-3 cell lines. Compounds \(\mathbf{21}_{\mathbf{c}}\), \(\mathbf{21}_{\mathbf{d}}\), and 24 exhibited high anti-proliferative activity, comparable to that of 5-fluorouracil. Additionally, ten compounds with potent anti-proliferative activities were further evaluated for their ability to inhibit TS enzyme. Six compounds (\(\mathbf{21}_{\mathbf{b}}\), \(\mathbf{21}_{\mathbf{c}}\), \(\mathbf{21}_{\mathbf{d}}\), 22, 23 and 24) demonstrated potent dose-related TS inhibition with \(\hbox {IC}_{50}\) values ranging from 1.57 to \(3.89\,\upmu \hbox {M}\). The in vitro TS activity results were consistent with those of the cytotoxicity assay where the most potent anti-proliferative compounds of the series showed good TS inhibitory activity comparable to that of 5-fluorouracil. Furthermore, molecular docking studies were carried out to investigate the binding pattern of the designed compounds with the prospective target, TS (PDB-code: 1JU6).     

Synthesis of novel 7-aryl and 7-spiropyrazolo[4′,3′:5,6]pyrido[2,3-<Emphasis Type="BoldItalic">d</Emphasis>]pyrimidine derivatives and their study as AChE inhibitors

An efficient route for the synthesis of novel 7-aryl and 7-spiropyrazolo[4\(^{\prime }\),3\(^{\prime }\):5,6]pyrido[2,3-d]pyrimidine derivatives is described. These compounds were obtained by a cyclocondensation reaction between pyrazolopyridinediamines 4 and aldehydes 5 or cyclic ketones 6 in the presence of acetic acid as catalyst. This procedure provides the desired compounds in good yields under a simple two-step methodology. The obtained compounds were evaluated as AChE inhibitors and showed weak AChe inhibition with \(\hbox {IC}_{50} = 115{-}470 \, \upmu \hbox {M}\).     

Synthesis of new quinazolin-2,4-diones as anti-<Emphasis Type="Italic">Leishmania mexicana</Emphasis> agents

The quinazolin-2,4-dione moiety is found in many compounds with important biological activities making it a target for its synthesis. In this work, a one-pot three-step synthesis of new quinazolin-2,4-diones from phthalic anhydrides and their activity against Leishmania mexicana are described. The new quinazolin-2,4-diones were isolated with yields in the range of 32–70 %. All compounds displayed lower cytotoxicity in RAW 264.7 macrophage over miltefosine. Compound 6,7-dichloro-3-phenylquinazoline-2,4(1H,3H)-dione (6e) displayed an attractive profile which includes anti-Leishmania mexicana activity (\(\hbox {IC}_{50} = 6.05\) \(\upmu \)M), much lower cytotoxic activity (\(\hbox {CC}_{50} = 111\) \(\upmu \)M) and a high selective index (\(\text {SI} = 18.35\)) proving to be superior to miltefosine.     

Ionic liquid-functionalized magnetic nanostructures as an efficient catalyst for the synthesis of 6H-chromeno[4,3-b]quinolin-6-ones

A novel imidazole ionic liquid (IL)-functionalized \(\hbox {silica}@\gamma \)-\(\hbox {Fe}_{2}\hbox {O}_{3}\) (\(\hbox {IL-SiO}_{2}@\hbox {MNP}\)) is prepared by the functionalization of \(\hbox {SiO}_{2}@\hbox {MNP}\) by 1-butyl-3-(3-trimethoxypropyl)-1H-imidazol-3-ium chloride as the IL moiety. The catalyst is characterized by transmission electron microscopy, scanning electron microscope, vibrating sample magnetometer, dynamic light scattering and Fourier transform infrared spectroscopy. \(\hbox {IL-SiO}_{2}@\hbox {MNP}\) showed good activity in the synthesis of 6H-chromeno[4,3-b]quinolin-6-one derivatives via multicomponent reaction of 4-hydroxycoumarin, anilines and benzaldehydes. The nanocatalyst is magnetically separable and easily recoverable and showed successful activity up to 10 runs.     

Photoreflectance spectroscopy of the chalcopyrite semiconductor <Emphasis Type="Bold">AgInS</Emphasis><Subscript>2</Subscript> for ordinary and extraordinary rays

Photoreflectance spectra have been measured on the chalcopyrite semiconductor silver indium disulfide (\(\hbox {AgInS}_{2}\)) for light polarization \({\varvec{E}}\) perpendicular (\({\varvec{E}} \bot {c}\)) and parallel to the c-axis (\({\varvec{E}} \vert \vert {c}\)) at temperature between 10 and 300 K. The measured photoreflectance spectra revealed distinct structures at 1.8–2.1 eV. The lowest bandgap energies \(E_{0A}\), \(E_{0B}\), and \(E_{0C}\) of \(\hbox {AgInS}_{2}\) show unusual temperature dependence at low temperatures (\(\le\)140 K). The \(E_{0\alpha }\) (\(\alpha =A, B, C\)) is found to increase with increasing temperature from 10 to \(\sim\)140 K and decreases with a further increase in temperature. This result has been successfully explained by taking into account the effects of thermal expansion and electron–phonon interaction. The spin–orbit and crystal-field splitting parameters of \(\hbox {AgInS}_{2}\) are determined to be \(\Delta _{{\mathrm{so}}}=38\) meV and \(\Delta _{{\mathrm{cr}}}=-168\) meV at T = 10 K, respectively, and are discussed from an aspect of the electronic energy band structure consequences. The temperature dependence of spin–orbit and crystal-field splitting parameters of \(\hbox {AgInS}_{2}\) was also presented.     

The envelope travelling wave solutions to the Gerdjikov–Ivanov model

Valence universal multireference coupled cluster (VUMRCC) method via eigenvalue independent partitioning has been applied to estimate the effect of three-body transformed Hamiltonian (\(\widetilde{{H}}_3\)) on ionisation potentials through full connected triple excitations \(S_{3}^{(1,0) }\). \(\widetilde{H}_3 \) is constructed using CCSDT1-A model of Bartlett et al for the ground-state calculation. Contribution of transformed Hamiltonian through full connected triples \(\overline{\widetilde{H}_3 S_3^{\left( {1,0} \right) }}\) involves huge amount of computational operations that is time-consuming. Investigation on \(\hbox {Cl}_{2}\) and \(\hbox {F}_{2}\) molecules using cc-pVDZ and cc-pVTZ basis sets shows that the above effect varies from 0.001 eV to around 0.5 eV, suggesting that inclusion of \(\overline{\widetilde{H} _3 S_3^{\left( {1,0} \right) } }\) is essential for highly accurate calculations.     

Synthesis and three-dimensional quantitative structure-activity relationship study of quinazoline derivatives containing a 1,3,4-oxadiazole moiety as efficient inhibitors against <Emphasis Type="BoldItalic">Xanthomonas axonopodis pv. citri</Emphasis>

A series of quinazoline derivatives containing a 1,3,4-oxadiazole moiety were synthesized and evaluated for their antibacterial activities against Xanthomonas axonopodis pv. citri (Xac) and Ralstonia solanacearum (Rs). Antibacterial bioassays indicated that most of target compounds exhibited significant antibacterial activities against Xac and Rs in vitro. Strikingly, compounds 6d–6i, 6m–6r and 6u–6x showed antibacterial activity against Xac, with \(\hbox {EC}_{50}\) values ranging from 14.42 to 38.91 \(\upmu \)g/mL, which are better than that of bismerthiazol (39.86 \(\upmu \)g/mL). Based on the antibacterial activity against Xac, comparative molecular filed analysis and comparative molecular similarity index analysis models were generated to investigate the structure-activity relationship of title compounds against Xac. The analytical results indicated that the above models exhibited good predictive accuracy and could be used as practical tools for guiding the design and synthesis of more potent quinazoline derivatives containing a 1,3,4-oxadiazole moiety.     

Facile synthesis and biological assays of novel 2,4-disubstituted hydrazinyl-thiazoles analogs

A convenient, one-pot multi-component synthesis of new 2,4-disubstituted hydrazinyl-thiazoles was accomplished using different aldehydes/ketones, thiosemicarbazide, and 4-methoxy phenacyl bromide in the presence of a catalytic amount of AcOH in EtOH. Products were obtained in reasonable yields and high purity. The in vitro antioxidant activity of hydrazinyl-thiazoles was evaluated by DPPH radical scavenging activity in comparison to ascorbic acid. Synthesized thiazoles 14c and 14g possessed the lowest \(\hbox {IC}_{50}\) values. Also, hydrazinyl-thiazoles were screened for their in vitro antibacterial activity against six strains of bacteria including S. aureus, M. luteus, E. coli, Ps. aeruginosa, B. subtilis, and A. hydrophila where some products showed good antibacterial activity. Moreover, compound 14a showed anticancer activity against melanoma cancerous cell lines A375 with \(\hbox {LC}_{50}= 0.55\hbox { mg}/\hbox {mL}\), slightly selective versus normal cell lines (Hu-2) with \(\hbox {LC}_{50}= 1.19\hbox { mg}/\hbox {mL}\).     

Strange quark star with Tolman IV background

In this paper, using the optical emission spectroscopy (OES) technique, the optical characteristics of a radiofrequency (RF) plasma jet are examined. The \(\hbox {Ar}/\hbox {O}_{2}\) mixture is taken as the operational gas and, the Ar percentage in the \(\hbox {Ar}/\hbox {O}_{2}\) mixture is varied from 70% to 95%. Using the optical emission spectrum analysis of the RF plasma jet, the excitation temperature is determined based on the Boltzmann plot method. The electron density in the plasma medium of the RF plasma jet is obtained by the Stark broadening of the hydrogen Balmer \(H_{\beta }\). It is mostly seen that, the radiation intensity of Ar 4p\(\rightarrow \)4s transitions at higher argon contributions in \(\hbox {Ar}/\hbox {O}_{2}\) mixture is higher. It is found that, at higher Ar percentages, the emission intensities from atomic oxygen (O) are higher and, the line intensities from the argon atoms and ions including O atoms linearly increase. It is observed that the quenching of \(\hbox {Ar}^{*}\) with \(\hbox {O}_{2}\) results in higher O species with respect to \(\hbox {O}_{2}\) molecules. In addition, at higher percentages of Ar in the \(\hbox {Ar}/\hbox {O}_{2}\) mixture, while the excitation temperature is decreased, the electron density is increased.     

Synthesis of first ever 4-quinolone-3-carboxylic acid-appended spirooxindole-pyrrolidine derivatives and their biological applications

A series of 4-quinolone-3-carboxylic acid-containing spirooxindole-pyrrolidine derivatives was synthesized via multicomponent 1,3-dipolar cycloaddition reactions of azomethine ylides with new (E)-4-oxo-6-(3-phenyl-acryloyl)-1,4-dihydroquinoline-3-carboxylic acids in good yields with high regioselectivity. The cycloadducts were characterized by analytical and spectral data including \(^{1}\hbox {H}\), \(^{13}\hbox {C}\), 2D NMR and mass spectroscopy. The structure of one of the compounds (8a) was investigated theoretically by computational techniques. DFT studies support the proposed mechanism for this cycloaddition reaction. Furthermore, antibacterial activities of the new compounds were evaluated against Gram-positive and Gram-negative bacterial strains. Compounds 8f, 8m and 8p showed potent inhibition activities against selected bacteria. The in vitro cytotoxicity of spirooxindole derivatives (8a–r) was evaluated against MCF-7 breast cancer cell line. Among the various compounds tested, compound 8f \((\hbox {IC}_{50} = 18.35~\upmu \hbox {M})\) showed significant cytotoxic activity compared to the standard drug doxorubicin \((\hbox {IC}_{50 }= 15.00~\upmu \hbox {M})\).     

On quantum analogue of dynamical stabilisation of inverted harmonic oscillator by time periodical uniform field

Quantum analogue of stabilised forced oscillations around an unstable equilibrium position is explored by solving the non-stationary Schrödinger equation (NSE) of the inverted harmonic oscillator (IHO) driven periodically by spatial uniform field of frequency \(\Omega \), amplitude \(F_{0}\) and phase \(\phi \), i.e. the system with the Hamiltonian of \(\hat{{H}}=(\hat{{p}}^{2}/2m)-(m\omega ^{2}x^{2}/2)-F_0 x\sin \) \(\left( {\Omega t+\phi } \right) \). The NSE has been solved both analytically and numerically by Maple 15 in dimensionless variables \(\xi = x\sqrt{m\omega /\hbar }\hbox {, }f_0 =F_0 /\omega \sqrt{\hbar m\omega }\) and \(\tau =\omega t\). The initial condition (IC) has been specified by the wave function (w.f.) of a generalised Gaussian type which suits well the corresponding quantum IC operator. The solution obtained demonstrates the non-monotonous behaviour of the coordinate spreading \(\sigma \left( \tau \right) \hbox { =}\sqrt{\big ( {\overline{\Delta \xi ^{2}\big ( \tau \big )} } \big )}\) which decreases first from quite macroscopic values of \(\sigma _{0} =2^{12,\ldots ,25}\) to minimal one of \(\sim \!(1/\sqrt{2})\) at times \(\tau <\tau _0 =0.125\ln \!\left( {16\sigma _0^4 +1} \right) \) and then grows back unlimitedly. For certain phases \(\phi \) depending on the \(\Omega /\omega \) ratio and \(n=\log _2\!\sigma _0 \), the mass centre of the packet \(\xi _{\mathrm {av}}( \tau )= \overline{\hat{{x}}(\tau )} \cdot \sqrt{m\omega /\hbar }\) delays approximately two natural ‘periods’ \(\sim \!(4\pi /\omega )\) in the area of the stationary point and then escapes to ‘\(+\)’ or ‘?’ infinity in a bifurcating way.  For ‘resonant’ \(\Omega =\omega \), the bifurcation phases \(\phi \) fit well with the regression formula of Fermi–Dirac type of argument n with their asymptotic \(\phi ( {\Omega ,n\rightarrow \infty } )\) obeying the classical formula \(\phi _{\mathrm {cl}} ( \Omega )=-\hbox {arctg} \, \Omega \) for initial energy \(E = 0\) in the wide range of \(\Omega =2^{-4},...,2^{7}\).     

Substituted <Emphasis Type="Italic">N</Emphasis>-aminothioglycolurils containing thiosemicarbazone moiety and their cytotoxic activity in vitro

A library of hybrid molecules bearing thioglycoluril and (hetero)aromatic aldehyde thiosemicarbazone moieties was synthesized via a tandem hydrazone formation—ring contraction reaction of 5,7-dialkyl-3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones with (hetero)aromatic aldehydes. All synthesized compounds were tested for their cytotoxic activity against rhabdomyosarcoma, A549, and MS human cancer cell lines by MTT-assay. Among the derivatives, (E)-4-benzylideneamino-1,3-dimethyl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one 1f was found to have the most marked antiproliferative activity toward the tested cell lines (1f: IC\(_{50}= 20.6,\) 23.7, and 6.4 \(\upmu \)M, respectively). The IC\(_{50}\) value of thioglycoluril 1f against normal human embryonic kidney cells HEK293 was 72.5 \(\upmu \)M, which appeared to be 3–11-fold higher than IC\(_{50}\) values of 1f against human cancer cells.     

Synthesis,insecticidal activities and structure–activity relationship study of dual chiral sulfilimines

To investigate the “methyl” impact on bioactivity of sulfiliminyl dicarboxamides, a total of 16 novel N-cyano and N-trifluoroacetyl sulfiliminyl dicarboxamides containing m-heptafluoroisopropylated aromatic amino moiety were studied. Two series of sulfiliminyl substituents were designed, synthesized and evaluated against oriental armyworm (Pseudaletia separata Walker) for their insecticidal activities. Their chemical structures were established by corresponding \(^{1}\hbox {H}\) NMR, HRMS and optical polarimetry. Bioassay results revealed that some of the title compounds showed potent insecticidal activities against oriental armyworm. Notably, compounds IIa, IIIa, IVa exhibited 100% activity at \(1\, \hbox {mg}\,\hbox {L}^{-1}\), in particular, IIa showed a comparable control efficacy to that of the commercial product flubendiamide. The SAR of these N-cyano sulfiliminyl isomers can be summarized as follows (Sc, Ss) \(\ge \) (Sc, Rs), while the N-trifluoroacetyl sulfiliminyl isomers is (Sc, Rs) \(\ge \) (Sc, Ss). Comparative molecular field analysis indicated that an electropositive substituent, \(\hbox {CH}_{3}\) group in the benzene ring was very important for the improvement in biological activity. These results could hold promise for novel chiral sulfiliminyl RyR regulators.     

Skeletal modifications of $$\upbeta $$-carboline alkaloids and their antiviral activity profile

To study the effect of the variation of fused ring size and substitution on the antiviral activity of \(\upbeta \)-carboline alkaloids, four types of structurally novel \(\upbeta \)-carboline alkaloids analogues, with indole-fused six- to nine-membered-rings motifs, were designed, synthesized, and evaluated for the inhibition of tobacco mosaic virus (TMV). Bioassay results indicated that most of these analogues had significant anti-TMV activity; especially I-14 (54 \(\pm \) 3 % at 500 \(\upmu \)g/mL in vitro; 51 \(\pm \) 2, 45 \(\pm \) 2, and 42 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vivo), II-4 (53 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vitro; 49 \(\pm \) 2, 57 \(\pm \) 2, and 48 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vivo), and II-8 (48 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vitro; 53 \(\pm \) 2 %, 56 \(\pm \) 2 %, and 46 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vivo), which were more potent vs. TMV than was ribavirin (36 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vitro; 37 \(\pm \) 2, 41 \(\pm \) 2, and 38 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vivo). The size of the fused ring has important effects on anti-TMV potency, which may be ascribed to conformational differences. The X-ray structures of I-1, I-6, II-8, and III show differing conformational preferences. The most potent compounds can be used as leads for further optimization as antiphytoviral agents.