Design, synthesis, spectral characterization and molecular docking studies of novel pyranoquinolinyl dihydropyridine carboxylates as potential antibacterial agents including Vibrio cholerae with minimal cytotoxity towards fibroblast cell line (L-929).

Novel pyranoquinolinyl dihydropyridine carboxylate (PDC) derivatives were designed by incorporating the multi-drug resistance modulating effects of 1,4 dihydropyridines along with potential antibacterial activity of quinolines in the molecular design. The designed PDC derivatives were synthesized by multi-step synthesis involving Michael addition, reduction followed by inverse electro demand Diels-Alder reaction to produce pyranoquinolinyl dihydropyridine carboxylates in good yields. All the PDC derivatives were characterized by 1H NMR, 13C NMR, FT-IR, Mass spectral and CHN analysis. The Quinolinyl dihydropyridine carboxylate derivatives were evaluated for in vitro antibacterial activity by agar well diffusion method. Molecular docking studies revealed that the exo diethyl 4-(4aR,5S,10bR)-5-(4-chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-8-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate diastereomer (5c) forms four hydrogen bonds with the cell wall protein of vibrio cholerae in comparison to the endo diethyl 4-((4aR,5R,10bR)-5-(4-chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-8-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate diastereomer (4c) which forms two hydrogen bonds with the cell wall protein of vibrio cholerae and hence leading to better anchorage, enhanced gold score and relatively good antibacterial activity for the exo PDC derivatives. Minimum inhibitory concentration (MIC) of the active compounds was evaluated by macro dilution method. The mechanism of antibacterial action of the PDC derivatives was investigated by SEM studies. The cytotoxicity of PDC derivatives were evaluated against fibroblast cells (L-929).

Cu-mediated synthesis of differentially substituted diazepines as AChE inhibitors; validation through molecular docking and Lipinski's filter to develop novel anti-neurodegenerative drugs.

A highly efficient Cu-mediated route for the synthesis of fused [1,2,3]triazolo[1,4]diazepines has been developed by azidation-cyclization of 2-bromo-N-propargylamines in a one-pot fashion. The key highlight of the present work is that the 2-bromo-N-propargylamines are prepared through the A3-reaction of cyclic amines such as isoquinoline and decarboxylative coupling of proline and pipecolinic acid with 2-bromo benzaldehyde and alkyne. As preliminary, these compounds were analyzed for their most probable bioactivity using various in silico tools. The recognized anti-neurodegenerative activity potential was assessed by molecular docking, AChE inhibition activity in erythrocytes and DPPH radical scavenging activity potentials possessed by the compounds. With a relative AChE inhibition activity of 97% (IC50 0.25 ±â€¯0.02 µM), compound 5d identified as the most active compound. Druggability of these compounds also evaluated through Lipinski's filter and other ADMET tools for the betterment of selective execution of in vitro and in vivo activities of the screened compounds cautiously.

Evaluation of Stress-Induced Microbial Siderophore from Pseudomonas aeruginosa Strain S1 as a Potential Matrix Metalloproteinase Inhibitor in Wound Healing Applications.

Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes capable of causing various inflammatory and various degenerative diseases if over-expressed. The active site of these enzymes is a zinc binding motif which binds to the specific site on the substrate and induce degradation. Hence an inhibitor is required to form a complex with zinc motif which hampers the binding ability of MMPs. To obtain novel MMPs inhibitor for wound healing, the chelating activity of siderophore from the microbial source was focused. During screening for siderophore production, strain S1 produced the highest amount of siderophore in the minimal salts medium. The isolate was confirmed as Pseudomonas aeruginosa strain S1 based on 16S rRNA gene sequencing and phylogenetic analysis. The activity of the siderophore was assayed using chrome azurol sulphonate and purified by the chromatographic techniques. The structural evidence through Fourier transform infrared and nuclear magnetic resonance spectra revealed that the isolated siderophore is a catecholate type with the distinctive characters. The positive results of calcein and fluozin-3 assays indicate that siderophore could bind to divalent metal ions, namely Fe(2+) and Zn(2+). As the siderophore compound focused on wound healing property, the in vitro studies revealed the viability of NH3T3 fibroblast cells and its efficiency in matrix modulating was confirmed through gelatin zymogram.

Synthesis of BF3 catalyzed Mannich derivatives with excellent ee from phenylpropanolamine, study of their antimicrobial activity and molecular docking.

Antimicrobial agents 4a-g and 5a-g with very good potency were synthesized with 100% ee from phenylpropanolamine (norephedrine) by BF3 catalyzed three components one pot Mannich reaction in good yields. Obtained compounds were characterized using spectral techniques. Antimicrobial study of these compounds revealed a good to very high potential activity against tested microbes when compared to standard antimicrobial drugs streptomycin and ketoconazole. These synthesized compounds exhibited significant minimum inhibitory concentration (MIC) values against Gram positive and Gram negative bacteria. Amongst compound 4b, 4c, 4d, 4e, 5a, and 5e exhibited very high potent MIC values against tested twelve bacteria and three fungi when compared to control. When subjected to molecular docking, in silico studies revealed significant binding energies ranging from -7.06 to -8.90 kcal/mol for all obtained compounds towards target receptor DNA topoisomerase IV and amongst compounds 4b and 4d have shown maximum binding energies 8.70 and 8.90 kcal/mol, respectively.

Synthesis, antimicrobial and molecular docking studies of enantiomerically pure N-alkylated ß-amino alcohols from phenylpropanolamines.

Enantiomerically pure N-alkylated ß-amino alcohols 1a, 1a', 1c, 1c', 1d, 1d', 1e and 1e', with ee 100% have been synthesized from phenylpropanolamines 2. Effect of the neighboring chiral environment on the newly formed chiral center has been studied experimentally and concluded that the newly formed chiral center's absolute configuration is opposite to the adjacent (α- or ß-) chiral environment. The antimicrobial activity of the synthesized ß-amino alcohols were screened using in vitro disc diffusion method and variable antimicrobial activities were shown for 1a, 1a', 1c, 1c', 1d, 1d', 1e &1e' and amongst them 1d &1d' exhibited significant activity against bacteria and fungi. In silico studies revealed all the synthesized ß-amino alcohols 1a-e and 1a'-e' have shown good binding energies ranging from -7.38 to -6.09 kJ/mol towards the target receptor DNA topoisomerase IV and 1d' has shown maximum binding energy -7.38 kJ/mol.

Methyl 4-(4-bromo-anilino)-2',5-dioxo-5H-spiro-[furan-2,3'-indoline]-3-carboxyl-ate.

In the title compound, C19H13BrN2O5, the spiro furan ring is almost planar with a maximum deviation of 0.034 (2) Å. The indole unit and the furan ring are normal to each other, making a dihedral angle of 87.82 (8) °. The mol-ecular structure is stabilized by an intra-molecular N-H⋯O hydrogen bond, which generates an S(6) ring motif. In the crystal, mol-ecules are linked via pairs of N-H⋯O hydrogen bonds, forming inversion dimers enclosing R (2) 2(8) ring motifs.

Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line.

Novel dispirooxindole-pyrrolidine derivatives have been synthesized through 1,3-dipolar cycloaddition of an azomethine ylide generated from isatin and sarcosine with the dipolarophile 3-(1H-indol-3-yl)-3-oxo-2-(2-oxoindolin-3-ylidene)propanenitrile, and also spiro compound of acenaphthenequinone obtained by the same optimized reaction condition. Synthesized compounds were evaluated for their antimicrobial activity and all the compounds shown significant activity. Anticancer activity was evaluated against A549 human lung adenocarcinoma cancer cell lines. Compounds 7b, 7g, 7i and 7r exhibit very good anticancer activity 62.96%, 62.03%, 67.67% and 60.22%, respectively, at the dose of 200µg/mL and compound 7i shows IC50 value in 50µg/mL.

Cu(OTf)2 catalyzed three component reaction: efficient synthesis of spiro[indoline-3,4'-pyrano[3,2-b]pyran derivatives and their anticancer potency towards A549 human lung cancer cell lines.

Cu(OTf)2 catalyzed efficient synthesis of spiropyrano[3,2-b]pyran-4(8H)-ones is accomplished via one-pot three component reaction between isatin, kojic acid and active methylenes. This synthetic protocol is operationally simple and affords product with good to excellent yields at a short reaction time. The synthesized compounds were evaluated for their tumor cell growth inhibitory activity against the human lung cancer cell line (A549) and found that 13 compounds exhibited moderate to good anticancer potency. Molecular docking studies were performed for all the synthesized compounds and the results showed that compound 4e showed greater affinity for anaplastic lymphoma kinase (ALK) receptor.

Diethyl [(2-chloro-anilino)(1,3-diphenyl-1H-pyrazol-4-yl)meth-yl]phospho-nate.

In the title compound, C(26)H(27)ClN(3)O(3)P, the mean plane of the central pyrazole ring forms a dihedral angle of 71.37 (14)° with the chloro-phenyl ring. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers with R(2) (2)(10) ring motifs. The 3-phenyl ring is disordered with four C atoms occupying two sets of sites with an occupancy ratio of 0.748 (4):0.252 (4).

5-(3-Meth-oxy-phen-yl)-3-phenyl-1,2-oxazole.

In the title compound, C16H13NO2, the isoxazole ring makes dihedral angles of 17.1 (1)° with the 3-meth-oxy-phenyl ring and 15.2 (1)° with the phenyl group. Centrosymmetric dimers that are realised by pairs of C-H⋯π inter-actions are observed in the crystal structure.

Methyl 4-anilino-2',5-dioxo-1',2'-di-hydro-5H-spiro-[furan-2,3'-indole]-3-carboxyl-ate.

In the title compound, C19H14N2O5, the spiro junction links an oxindole moeity and a furan ring, which subtend a dihedral angle of 83.49 (6)°. The mol-ecular structure features an N-H⋯O hydrogen bond, which generates an S(6) ring motif. The crystal packing is governed by two N-H⋯O inter-actions, one of which generates a centrosymmetric R 2 (2)(14) dimer. The other N-H⋯O inter-action along with a C-H⋯O hydrogen bond contributes to the formation of a C 2 (2)[R 2 (2)(9)] dimeric chain running along the b-axis direction.

1'-Butyl-2-methyl-1',2,2',3,4,9-hexa-hydro-spiro-[benzo[f]isoindole-1,3'-indole]-2',4,9-trione.

In the title compound, C(24)H(22)N(2)O(3), the indoline and pyrrole-fused naphtho-quinone units are both essentially planar [r.m.s. deviations = 0.042 (3) and 0.133 (3) Å, respectively]. The pyrrole ring adopts a C-envelope conformation. The dihedral angle between the mean planes of the two five-membered rings is 89.94 (9)°. The O atoms deviate from the mean planes of the pyrrolidine and naphthalene rings by 0.0311 (2), 0.2570 (2) and 0.1669 (2) Å. In the crystal, C-H⋯O inter-actions generate dimers with R(2) (2)(16) and R(2) (2)(18) graph-set motifs. The carbonyl O atom is involved in bifurcated hydrogen bonding. C-H⋯π inter-actions also occur.

(E)-3-Phenyl-2-(1-tosyl-1H-indol-3-ylcarbon-yl)acrylonitrile.

In the title compound, C(25)H(18)N(2)O(3)S, the indole moiety is planar and makes a dihedral angle of 89.95 (09)° with the phenyl ring of the sulfonyl substituent. The mol-ecular conformation features a weak C-H⋯N short contact and the crystal packing reveals a weak C-H⋯O hydrogen bond.

Diethyl [(2-bromo-anilino)(1,3-diphenyl-1H-pyrazol-4-yl)meth-yl]phospho-nate.

In the title compound, C(26)H(27)BrN(3)O(3)P, the central pyrazole ring forms a dihedral angle of 71.7 (2)° with the bromo-phenyl ring. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers with R(2) (2)(10) ring motifs. Four C atoms of the 3-phenyl ring are disordered over two sets of sites [site occupancies = 0.745 (6) and 0.225 (6)].

2-Iodo-3-(4-meth-oxy-anilino)-5,5-dimethyl-cyclo-hex-2-en-1-one.

The cyclo-hexene ring in the title compound, C(15)H(18)INO(2), adopts a sofa conformation. The dihedral angle between the cyclo-hexene (through all ring atoms) and benzene rings is 63.3 (1)°. The mol-ecular conformation features an N-H⋯I short contact and the crystal packing features C-H⋯O hydrogen bonds.

Ethyl 2-benzyl-3-[3-(4-chloro-phen-yl)-1-phenyl-1H-pyrazol-4-yl]-4,6-dioxo-5-phenyl-octa-hydro-pyrrolo-[3,4-c]pyrrole-1-carboxyl-ate.

The title compound, C(37)H(31)ClN(4)O(4), crystallizes with two mol-ecules (A and B) in the asymmetric unit. The pyrrole rings in both mol-ecules are connected via cis fusion, whereas one ring has a twisted conformation and the other assumes a half-chair conformation. In the crystal, the A mol-ecules form inversion dimers via a pair of C-H⋯Cl inter-actions, while the B mol-ecules form chains propagating in [1[Formula: see text]0], via C-H⋯O inter-actions. In the crystal, there are also a number of C-H⋯π inter-actions present.

3-(1,2-Di-p-tolyl-vin-yl)-2-methyl-1H-indole.

In the title compound, C(25)H(23)N, the indole unit makes a dihedral angles of 79.03 (5) and 61.82 (4)° with the benzene rings. No classical hydrogen bonds are found in the crystal structure.

5-(3-Methyl-phen-yl)-3-phenyl-1,2-oxazole.

In the title compound, C(16)H(13)NO, the isoxazole ring makes dihedral angles of 16.64 (7)° with 3-methyl-phenzyl ring and 17.60 (7)° with the unsubstituted phenyl ring.

cis-6-Bromo-4-(1-methyl-1H-indol-3-yl)-10,10a-dihydro-1H,4H-2,9-dioxa-3-aza-benz[f]azulene.

In the title compound, C(20)H(17)BrN(2)O(2), the seven-membered oxepine ring adopts a chair conformation. The indole moiety is essentially planar with a maximum deviation of 0.031 (3)Å. The indole ring system forms a dihedral angle of 21.87 (8)° with the mean plane of the 10-membered heterobicycle. The crystal packing is stabilized by inter-molecular C-H⋯O and C-H⋯π inter-actions.

2-Methyl-3-{2-nitro-1-[2-(prop-2-yn-1-yl-oxy)phen-yl]eth-yl}-1H-indole.

In the title compound, C(20)H(18)N(2)O(3), the indole unit is essentially planar, with a maximum deviation of 0.0197 (18) Šfor the N atom and forms a dihedral angle of 78.09 (9)° with the propyne-subsituted phenyl ring. The propyne group is almost linear, the C-C C angle being 176.5 (2)°, and is also in the flagpole position on the O atom. In the crystal, mol-ecules are linked via N-H⋯O and C-H⋯O inter-molecular hydrogen bonds involving the nitro-group O atoms as acceptors.