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Abstract In the present study, a series of novel and biologically potent 6-amino-1-(2,4-dinitrophenyl)-4-phenyl-1,4-dihydropyrano [2,3-c]pyrazole-5-carbonitrile derivatives (5a-5u) have been synthesized through multicomponent reaction between various substituted aromatic aldehyde derivative (4a - 4u), 2, 4-dinitrophenyl hydrazine (1), ethyl acetoacetate (2) and malononitrile (3) in the presence of SnCl 2 as a prompt catalyst using both microwave irradiation method as well as conventional method. The structure of synthesized compounds were confirmed by various spectroscopic methods such as 1H NMR, 13C NMR, IR, Mass analysis and elemental analysis. All the synthesized compounds were subjected in vitro antibacterial, anti-tuberculosis screening and cytotoxicity MTT assay. In vitro biological study revealed that the synthesized compound 5a, 7a and 8a are showing good anti-bacterial and anti-tuberculosis activity. The in silico study of ADME pharmacokinetic properties were also predicted for synthesized compounds for checking their bioavailability. Furthermore, molecular docking study of synthesized compounds with enoyl-ACP reductase (oxidoreductase) was carry out to find out the binding affinity of compounds. Docking study demonstrated that compound 7b and 7a possessed superior binding affinity with target enzyme by strong hydrogen bonding. We have also carried out molecular dynamics simulation to check the stability of docked complex, conformational changes and primary molecular interaction. Graphical abstract Image 1 Highlights • Synthesis, characterization of targeted compounds. • Potent activity against TB H 37 Rv. • Molecular docking and Dynamics study. [ABSTRACT FROM AUTHOR]

• A series of new pyrano[2,3- c ]pyrazole and pyrazolo[4′,3′:5,6]pyrano[2,3- d ]pyrimidine derivatives were synthesized using facile green approach in excellent yields. • Compound M2 was isolated as an un expected novel compound. • The antimicrobial, antioxidant, and anti-cancer activities of the titled compounds were evaluated in vitro and most of the compounds manifested auspicious biological outcomes. • Compound M21 was the most promising anti-bacterial agent with potential binding affinity against the penicillin-binding protein. • Compound M5 was the most cytotoxic compound with potential binding affinity against CDK2 proteins. An eco-friendly approach was conducted for synthesizing pyrano[2,3- c ]pyrazoles M1 - M25 via a one-pot reaction of hydrazine hydrate 99%, ethyl acetoacetate or diethyl malonate, carbonyl group source, and active methylene compounds. Besides, pyrazolo[4′,3′:5,6]pyrano[2,3- d ]pyrimidines M26 - M31 was synthesized via intramolecular cyclization of M10 and M13. Thereafter, the antimicrobial, antioxidant, and anti-cancer activities of the titled compounds were evaluated utilizing an array of techniques. Fortunately, the vast majority of the compounds exhibited promising biological activities. Over and above, in silico study was employed to determine the expected mode of action of the synthesized compounds. M21 was the most promising anti-bacterial agent, while M5 was the most cytotoxic compound. Finally, DFT theoretical calculations were used to study the stability and structural parameters of the newly synthesized compounds. DFT calculations showed the energy gaps between the HOMO-LUMO with all the investigated compounds in a range of 4.04–5.66 eV allowing for easy exchange of electrons and the reactivity. [Display omitted] [ABSTRACT FROM AUTHOR]

• Wang-OSO 3 H was effective for the synthesis of pyrano[2,3- c ]pyrazole derivatives. • This sonochemical approach proceeded in pure water and catalyst was recyclable. • In silico / in vitro evaluation against SIRT1 identified 5i and 5l as promising hits. • in silico study indicated importance of H-bonding with ILE347 and ASP348. • Acceptable ADME properties were predicted for compound 5i and 5l. The pyrano[2,3- c ]pyrazole framework was explored for the design and synthesis of compounds as potential inhibitors of SIRT1. The feasibility of this strategy was reasoned by the unique structural features of this scaffold and the reported cytotoxicity of compounds containing this framework. The sonochemical synthesis of target compounds was accomplished by using the Wang resin (Wang-OSO 3 H) as a recoverable catalyst under eco-friendly conditions. Thus, the desired 4-substituted 6-amino-3-methyl-1,4-dihydropyrano[2,3- c ]pyrazole-5-carbonitrile derivatives were prepared via a 4-component reaction of β -ketoester, hydrazine, aldehyde and malononitrile in pure water in good yields. The recyclability of the catalyst was demonstrated successfully. All the synthesized compounds were initially assessed in silico against the targeted protein i.e. hSIRT1 that indicated compound 5i and 5l along with several other compounds as possible inhibitors. Both of these compounds participated in two vital H-bond interactions with the residue GLN345 and ASN346 in silico that was reflected in their estimated total energy. In vitro assessment of these pyrano[2,3- c ]pyrazoles against SIRT1 revealed encouraging inhibitory activities (> 50% inhibition) that was in agreement with the results of docking studies. Indeed, 5i and 5l were identified as the most active compounds in this series. The Structure-Activity-Relationship (SAR) study suggested important role of the C-4 aryl substituent along with the N-1 phenyl ring of the pyrano[2,3- c ]pyrazole moiety in the SIRT1 inhibitory activities of this class of compounds. Thus, a OH or Cl group at the p -position of the C-4 benzene ring together with the N-1 phenyl moiety appeared to be beneficial for activity. Overall, the initial design and then sonochemical synthesis followed by in silico as well as in vitro studies allowed identification of pyrano[2,3- c ]pyrazole based small molecules as potential inhibitors of SIRT1. [Display omitted] The design and sonochemical synthesis followed by in silico as well as in vitro studies allowed identification of pyrano[2,3- c ]pyrazole based small molecules as potential inhibitors of SIRT1 [ABSTRACT FROM AUTHOR]

• Synthesis of dihydropyrano[2,3-c]pyrazoles in high yields and short reaction times. • IRMOF-3/GO/CuFe 2 O 4 nanocomposite is introduced as a new and superior catalyst. • IRMOF-3/GO/CuFe 2 O 4 was identified using different spectroscopic analysis. • The heterogeneous catalyst can be easily recycled with a slightly decrease in its activity. In the present study, we reported a facile and cost-effective method for synthesizing magnetic copper ferrite nanoparticles supported on IRMOF-3/GO [IRMOF-3/GO/CuFe 2 O 4 ]. The prepared IRMOF-3/GO/CuFe 2 O 4 was completely characterized by various spectroscopic techniques such as Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), X-ray diffraction (XRD), infrared spectroscopy (IR), thermogravimetric (TGA), energy-dispersive X-ray spectroscopy, and elemental meapping. The synthesized nanocatalyst demonstrated high catalytic activity in the synthesis of dihydropyrano[2,3-c]pyrazoles via a one-pot reaction of hydrazine hydrate, acetylene ester, aryl aldehydes, and malononitrile exposed to ultrasound irradiations. In comparison to formerly reported approaches, this protocol has various advantages including wide substrate compatibility, short reaction times, excellent yields, little catalyst loading, good reusability, and high efficiency. The catalyst was separated by simple filtration and after several rounds of reuse and recovery, the amount of activity in this catalytic system remained nearly constant. [ABSTRACT FROM AUTHOR]

Abstract: We developed an efficient and simple one-pot synthesis of functionalized multi-substituted 2,4-dihydro-pyrano[2,3-c]pyrazole dicarboxylates from β-ketoesters, hydrazine, dimethyl acetylenedicarboxylate and malononitrile in EtOH. This four-component one-pot reaction carried out in the presence of DABCO catalyst showed advantages over a one-pot three-component method in its simple procedure, high yield and low toxicity. [Copyright &y& Elsevier]

Abstract: Cocamidopropyl betaine (CAPB) as a biodegradable surfactant produces a new worm-like micellar medium for rapid synthesis of dihydropyrano[2,3-c]pyrazoles via a four-component reaction of aldehydes, ethyl acetoacetate, malononitrile, and hydrazine hydrate at 50–60°C. This zwitterionic surfactant was superior to anionic, cationic, and nonionic alternatives for accessing high yields of pure products without the use of any organic solvent. While the reaction medium was reusable, simple isolation of products, mild reaction conditions, low loading of CAPB for critical micelle concentration and short reaction times are additional advantages of this green procedure. [Copyright &y& Elsevier]

Highlights: [•] Dihydro-pyrano[2,3-c]pyrazoles were synthesized with aromatic aldehydes obtained from lignin. [•] The synthesis of dihydro-pyrano[2,3-c]pyrazoles was carried out with microwave-assisted technology. [•] The syringyl substituted compounds exhibited very potent antioxidant activity. [•] Those compounds possessed low cytotoxicity. [•] Their structure–activity relationship (SAR) was studied. [•] It provided an effective approach for value-added application of lignin. [ABSTRACT FROM AUTHOR]

Highlights: [•] First four-component biocatalytic reaction in organic synthesis. [•] First lipase catalyzed synthesis of biologically important dihydropyrano[2,3-c]pyrazole core. [•] First catalytic application of lipase from Aspergillus niger in a multicomponent reaction. [•] Catalytic efficiency, recyclability, and effect of solvents were thoroughly studied. [•] Easy access of dihydropyrano[2,3-c]pyrazoles from less reactive aliphatic aldehydes and ketones. [Copyright &y& Elsevier]

Abstract: A green and efficient one-pot, four-component synthesis of methyl 6-amino-5-cyano-4-aryl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylates in water is described. The method is catalyst-free, atom-economical, and does not involve tedious work-up or purification affording the target compounds in good yields. [Copyright &y& Elsevier]

Abstract: The enantioselective tandem Michael addition–cyclization reaction between 3-methyl-2-pyrazolin-5-one and benzylidenemalononitriles was studied with modularly designed organocatalysts (MDOs) to yield 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles in high yields and moderate to good enantioselectivities. Most importantly, a new catalytic mode of the MDOs was established. Instead of being used as a nucleophile to form an enamine intermediate, the reaction center modules (amino acids) of the MDOs are now used as a Lewis base in this base-catalyzed reaction. Since there are more reactions catalyzed by Lewis bases than by the enamine mechanism, this finding greatly expands the scope of the MDOs in organic reactions. On the other hand, because the stereocontrolling modules (cinchona alkaloid derivatives) themselves may be used as Lewis base catalysts, this new method may also be viewed as an expeditious way for the modification of the reaction center of the cinchona alkaloid catalysts. [Copyright &y& Elsevier]

Abstract: A tetrabutylammonium hydrogen sulfate (TBA-HS) mediated procedure for one pot synthesis of novel benzopyran-annulated pyrano[2,3-c]pyrazoles via domino/Knoevenagel-hetero-Diels–Alder reaction has been demonstrated. [Copyright &y& Elsevier]

Abstract: Pyrrolo[3,4-c]pyrazole-4,6(1H,5H)-dione, pyrano[2,3-c]pyrazole-5-carbonitrile, pyrano[2,3-d]4-imidazolines, pyrido[2,1-b]benzimidazole, pyrido[2,1-b][1,3]benzoxazole, pyrido[2,1-b][1,3]benzothiazole and pyrido[2,1-b]quinazoline were synthesised from antipyrine derivatives with appropriate reagents such as maleimides, malononitrile, ethyl cyanoacetate, benzimidazole-2-acetonitrile, benzothiazole-2-acetonitrile, benzoxazol-2-acetonitrile, benzoylacetonitrile and other reagents. The newly synthesised compounds were established by elemental analysis, spectral data, and alternative synthetic routes whenever possible. [Copyright &y& Elsevier]

• A novel composite including graphene oxide nano-sheets and zinc oxide nanoparticles. • High catalytic activity of Fe 3 O 4 /GO@melamine-ZnO in multicomponent synthesis reactions. • Excellent intercalation of ZnO nanoparticles between 2D nano-sheets. • Well functionalization of graphene oxide nano-sheets with melamine as cross-linkers. • Super capacitive behavior of Fe 3 O 4 /GO@melamine-ZnO nanocomposite. Herein, an efficient versatile nanocomposite constructed of melamine-functionalized graphene oxide nano-sheets (GO@melamine), iron oxide nanoparticles (Fe 3 O 4 NPs), and zinc oxide (ZnO NPs) is presented. Moreover, two different applications have been studied for the prepared Fe 3 O 4 /GO@melamine-ZnO nanocomposite: First, as a heterogeneous catalyst for synthesis of pyrano[2,3-c]pyrazole derivatives in short reaction time (10 min) with high yields (96 %), second, as a substantial electrical supercapacitor with typical capacitive behavior, high resistance, and excellent electrode stability. From the catalytic aspect, high effectiveness, convenient isolation, and significant reusability could be referred as the distinguished properties for the produced nanocomposite. Turn-over number (TON) and turn-over frequency (TOF) values for the presented catalytic system have been estimated 17.2 × 106 and 1.71 × 106 min−1, respectively, which revealed high catalytic performance of this catalytic system. From electrochemical aspect, economic benefits for fabrication of the introduced nanocomposite containing low-cost materials, make it as a suitable electrical supercapacitor for industrial applications. [ABSTRACT FROM AUTHOR]