Now day; the interest for the synthesis of heterocyclic compounds containing hydroquinoline fragments has increased tremendously due to their wide variety of pharmaceutical and industrial applications. This work details the synthesis of linear and fused heterocyclic systems containing hydroquinoline fragments and the pharmacological activity spectra of the synthesized compounds was predicted by in silico method using Prediction of Activity Spectra of Substances (PASS) program. 1,2,2,4-tetramethyl-1,2-dihydroquinoline-6-carbaldehyde 5a was reacted for three hours with a system of hydroxylammonium chloride/pyridinium chloride/toluene to produce 1,2,2,4-tetramethyl-1,2-dihydroquinoline-6-nitrile 7. N-benzyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehyde 6b and iodine reacted at room temperature in aqueous ammonia water, followed by aq. treatment with Na2S2O3 and produced N-benzyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-nitrile 8. 30-60% 2-phenyl-1,3-oxazol-5(4H)-ones 9a,b; 10a,b were synthesized via the condensation reaction of N-alkylhydroquinoline-6-carbaldehydes 5a,b; 6a,b with hippuric acid in acetic acid. When activated 7-methylazolopyrimidines 11a,b were reacted with N-alkyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehydes 6a,b, the reaction produced 60–70% yield of 7-[(E)-2,2,4-trimethylhydroquinolin-6-ylidenemethyl]azolo[1,5-a]pyrimidin-6-yl carboxylic acids 12a,b. The condensation reaction of 7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 3h with dimethylacetylenedicarboxylate (DMAD) and ethylacetoacetate afforded methyl (Z)-2-(5,7,7,8-tetramethyl-2-oxo-7,8-dihydrofuro[3,2-g]quinolin-3(2H)-ylidene)acetate 16 and 4,6,8,8,9-pentamethyl-8,9-dihydro-2H-pyrano[3,2-g]quinolin-2-one 17, respectively. The condensation reaction of 6-formyl-7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 5e with methylene active compounds ethylcyanoacetate/dimethyl-3-oxopentanedioate/ ethylacetoacetate/diethylmalonate/Meldrum’s acid afforded 3-substituted dihydroquinoline containg coumarins 19 & 21. A pentacyclic coumarin 22 was obtained via the random condensation reaction of malononitrile with 5e in the presence of catalytic amount of piperidine in ethanol. The potential biological activities of the synthesized compounds were evaluated using PASS computer program. According to the prognosis, (E)-4-(N-alkylhydroquinolin-6-yl)-3-buten-2-ones, 13a, b & 14 showed high probability of being active (Pa) as the Gluconate 2-dehydrogenase inhibitor, Anti-allergic, Anti-asthmatic, and Anti-arthritic with the Pa value of 0.849-0.870. It was also found out that hydroquinolinecarbonitrile compounds 7 & 8 have a propensity to act as a good progesterone antagonists, anti-allergic, anti-asthmatic, and anti-arthritic (Pa = 0.276-0.827). Among the coumarin moieties containing hydroquinolines, compounds 17, 19a, and 19c were predicted to be good progesterone antagonists with the Pa values of 0.710, 0.630 and 0.615; respectively.

Synthesis and antitumour activity of a palladium compound, [Bis (quinoline) palladium (II) chloride] (coded as NH1) alone and in combination along with its proposed mechanism of action has been described in the present study. Antitumour activity has been performed in seven different cancer cell lines using colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The investigated palladium compound demonstrated superiority over clinical standard cisplatin against drug resistant ovarian cancer cell lines. NH1 also demonstrates 4.4 times greater activity than cisplatin against breast cancer model. Binary sequenced combination study showed that NH1 in combination with curcumin is mostly additive to antagonistic. However, combination of NH1 with 6-shogaol demonstrated synergism depending on dose and sequence. Proteomic study revealed that changes in expression of 14 proteins were significantly associated with anticancer mechanism of NH1. In vivo anticancer activity of NH1 at a dose of 0.75 mg/kg was also evaluated using Erlich Ascites Carcinoma (EAC) cell lines in Swiss-albino mice model. Preliminary toxicity study in Swiss-albino mice proved that NH1 is comparatively less toxic at both of the administered doses, either 2.5 mg/kg or 5 mg/kg. However, cisplatin demonstrated significant toxicity at both of the administered doses. Biochemical investigations also supported that NH1 demonstrated lesser toxicity profile towards liver or kidney compared to clinical standard cisplatin.

Quadruplex-interactive small molecules have a wide potential application, not only as drugs but also as sensors of quadruplexes structures. The purpose of this work is the synthesis of analogues of the bis-methylquinolinium-pyridine-2,6-dicarboxamide G4 ligand 360A, to identify relevant structure-activity relationships to apply to the design of other G4-interactive small molecules bearing bis-quinoline or bis-isoquinoline moieties. Thermal denaturation experiments revealed that non-methylated derivatives with a relative 1,4 position between the amide linker and the nitrogen of the quinoline ring are moderate G4 stabilizers, with a preference for the hybrid h-Telo G4. Insertion of a positive charge upon methylation of quinoline/isoquinoline nitrogen increases compounds capacity to selectively stabilize G4s compared to duplex DNA, with a preference for parallel structures. Among these, compounds having a relative 1,3-position between the charged methylquinolinium/isoquinolinium nitrogen and the amide linker are the best G4 stabilizers. More interestingly, these ligands showed different capacities to selectively block DNA polymer-ization in a PCR-stop assay and to induce G4 conformation switches of hybrid h-Telo G4. Mo-lecular dynamic simulations with the parallel k-RAS G4 structure showed that the relative spatial orientation of the two methylated quinoline/isoquinoline rings determines the ligands mode and strength of binding to G4s.

The compound, C27H23N3 (1), crystallizes in the triclinic system of the P-1 space group. The unit cell comprises a dimer of 1, in which the monomers are linked by two complementary hydrogen bonds between N1 and H1-C1 of another molecule. The dimers form chains along the a-axis through intermolecular interactions between the N2 acceptor atoms and C17 donors from molecules in the nearest neighbouring dimer. These interactions form extended sheets of the dimers of 1, along the ab plane. The quinolinylmeth-2-yl groups of 1 lie in almost orthogonal planes and their N1/2(q) donor atoms being away from the apical amino N3 atom.

Looking for effective synthetic methods for 1H-pyrazolo[3,4-b]quinolines preparation, we came across a procedure where in a three component reaction catalyzed by L-proline, 4-aryl-4,9-dihydro-1H-pyrazolo[3,4-b]quinolines are formed. These compounds can be easily oxidized to a fully aromatic system, which gave hope for a synthetic method that could replace e.g. Friedländer condensation, often used for this purpose, although severely limited by the availability of suitable substrates. However, after careful repetition of the procedures described in the publication, it turned out that the compounds described therein do not form at all. The actual compounds turned out to be 4,4-(phenylmethylene)-bis-(3-methyl-1-phenylpyrazol-5-oles). 4-Aryl-4,9-dihydro-1H-pyrazolo[3,4-b]quinolines were prepared by another method and used as standards to compare the products formed in the original procedure.