A synthesis of 4-methylpyrano[2,3-e]indole-2,8,9-trione (5) is achieved from 7-amino-4- methylcoumarin by adopting the classical Sandmeyer methodology. The cyclocondensation reaction of pyrano-isatin 5 with the appropriately substituted o-phenylenediamines 6 in polyphosphoric acid proceeded regioselectively to furnish the respective pyrano[2’,3’:4,5]indolo[2,3-b]quinoxalines 7a - c. Structural assignments of the new compounds are based on microanalytical and spectral (IR, MS and NMR) data.

A group of new amidrazone compounds that include a quinoline component was produced through the reaction of hydrazonyl chloride, derived from 6-aminoquinoline, with appropriate secondary cyclic amines. The new compounds were confirmed through 1H-NMR, 13C-NMR, FTIR, and HRMS, and further verified by single-crystal X-ray diffraction. The antitumor potential of the synthesized compounds was tested against lung cancer (A549) and breast cancer (MCF-7) cell lines. Among the compounds, the ethyl carboxylate and o-hydroxy phenyl piperazine derivatives (10d and 10g) exhibited the strongest activity against both cell lines, with IC50 values of 43.1 and 59.1 μM for the lung and breast cancer cell lines, respectively. Moreover, the most potent compounds were subsequently docked into the c-Abl kinase binding site (PDB code: 1IEP) as a possible anticancer mechanism. In-silico ADMET study shows acceptable pharmacokinetic properties, and the toxicity profile for the most potent compounds is non-carcinogenic.

The study aims to assess the interaction between fluconazole and sulfonatocalix[4]naphthalene towards enhancing its dissolution performance and antimycotic activity. A solubility study was carried out at different pH conditions, and the results revealed the formation of a 1:1 molar ratio fluconazole-sulfonatocalix[4]naphthalene inclusion complex with an A_L type phase solubility diagrams. The solid powder systems of fluconazole-sulfonatocalix[4]naphthalene were prepared using kneaded and co-evaporation techniques and physical mixtures. DCS, PXRD, TGA-DTG, FT-IR, and in vitro dissolution performance characterize the prepared systems. According to physicochemical characterization, the co-evaporation approach produces an amorphous inclusion complex of the drug inside the cavity of sulfonatocalix[4]naphthalene. The co-evaporate product significantly increased the drug dissolution rate up to 93 ± 1.77% within 10 min, unlike other prepared solid powders. The antimycotic activity showed an increase substantially (p ≤ 0.05, t-test) antimycotic activity of fluconazole co-evaporate mixture with sulfonatocalix[4]naphthalene compared with fluconazole alone against clinical strains of Candida albicans and Candida glabrata. In conclusion, sulfonatocalix[4]naphthalene could be considered an efficient complexing agent for fluconazole to enhance its aqueous solubility, dissolution performance, and antimycotic activity.

A model N-ethyl-1,10-dioxo-3-phenylpyrano[3,2- f ]quinoline-9-carboxylic acid (8) and the isomeric (2-substituted) pyrano[2,3- f ]quinoline-9-carboxylic acids (6 and 7) were prepared from the corresponding 6/7-aminochromen-4-ones via the Gould-Jacobs reaction. The new tricyclic heterocycles 6-8 exhibit moderate antibacterial activity (MIC=16 - 64 μgmL^-1) against E. coli and S. aureus