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Two series of N’(E)-heteroaromatic-isonicotinohydrazide derivatives (3a-f and 4a-b) and 1-(7-chloroquinolin-4-yl)-2-[(heteroaromatic)methylene]hydrazone derivatives (5a-f and 6a-b) have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. Several compounds were noncytotoxic and exhibited significant minimum inhibitory concentration (MIC) activity (3.12, 2.50, 1.25, or 0.60 μg/mL), which can be compared to that of the first-line drugs ethambutol (3.12 μg/mL) and rifampicin (2.0 μg/ml). These results can be considered an important starting point for the rational design of new leads for anti-TB compounds.

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Two series of pyrazinamide (PZA) derivatives have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. Some compounds exhibited minimum inhibitory concentration activity of 50–100 μg/mL, greater than the first line antituberculosis drug PZA in Alamar Blue assay (>100 μg/mL). The obtained activities can be considered promising results, which characterizes these compounds as good start points to development of new antitubercular agents.

A series of twenty-one 7-chloro-4-quinolinylhydrazones derivatives (3a-u) have been synthesized and evaluated for their cytotoxic potential against three cancer cell lines using MTT assay. The compounds 3b, 3e, 3f, 3h, 3j, 3n, 3r and 3u displayed more than 90% of growth inhibition (GI) and they were selected for in vitro anticancer activities evaluation against four human cancer cell lines. These results were expressed as the concentrations that induce 50% inhibition of cell growth (IC50) in μg/mL. Considering that, compounds 3b, 3e, 3h, 3n, 3r and 3u exhibited good cytotoxic activity against at least three cancer cell lines (0.7967-4.200 μg/mL). In general, we observed that the presence of electron-withdrawing groups in the benzene ring is important for the anticancer activity in this series, such as fluorine (3h), chlorine (3b) amd bromine (3e) groups in meta position and nitro group (3r) in para position. These derivatives could be considered interesting start points to develop a new anticancer drug and confirm the potential of chloroquine derivatives as lead compounds in anticancer drug discovery.

The molecules of 4-allyloxy-7-chloroquinoline, C(12)H(10)ClNO, (I), 7-chloro-4-methoxyquinoline, C(10)H(8)ClNO, (II), and 7-chloro-4-ethoxyquinoline, C(11)H(10)ClNO, (III), are all planar. In all three structures, π-π interactions between the quinoline ring systems are generated by unit-cell translations along the a axes, irrespective of space group. These structures are the first reported for 4-alkoxyquinolines.

The synthesis and anti-tubercular activity of series of acyl hydrazonyl compounds, namely (E)-N'-(arylidene)thiophen-2-carbohydrazide, (E)-N'-(arylidene)furan-2-carbohydrazide, (E)-N-methyl-N'-arylidenethiophen-2-carbohydrazide, and E)-N-methyl-N'-arylidene-2-(thien-2yl)-acetohydrazide, [32 compounds in all] are reported. The activities of against Mycobacterium tuberculosis H37Rv (ATTC27294) are compared with those (E)-N'-arylidene-2-(thien-2-yl)-acetohydrazide, previously reported. The most active compounds are (aryl = 5-nitrothien-2-yl), (aryl = 5-nitrofuran-2-yl) and (aryl = 5-nitrothien-2-yl). Moderate activity was displayed by (aryl = 5-nitrofuran-2-yl) and certain derivatives of series where aryl is pyridin-2-yl or an o-hydroxyphenyl derivative. Doubling of certain NMR signals of each compound in solution indicates that a mixture of conformers, Z C(O)NH /E (C=N) and E C(O)NH /E (C=N) about the C(O)-NH-N=C(H, aryl) fragment is present. In contrast, only one form for each compound is present in solution from the single set of NMR signals. It is suggested that this form in solution is the E C(O)NH /E (C=N) form. Only a single set of NMR signals are found for the N-methylated derivatives.

Quinoline derivatives and especially quinolones are considered as privileged structures in medicinal chemistry and are often associated with various biological properties. We recently isolated a series of original monoterpenyl quinolones from the bark of Codiaeum peltatum. As this extract was found to have a significant inhibitory activity against a Leishmania species, we decided to study the anti-leishmanial potential of this type of compound. Leishmaniasis is a serious health problem affecting more than 12 million people in the world. Available drugs cause harmful side effects and resistance for some of them. With the aim of finding anti-leishmanial compounds, we developed a synthetic strategy to access natural quinolones and analogues derived from zanthosimuline. We showed the versatility of this natural compound toward cyclization conditions, leading to various polycyclic quinolone-derived structures. The natural and synthetic compounds were evaluated against amastigote forms of Leishmania infantum. The results obtained confirmed the interest of this family of natural compounds but also revealed promising activities for some intermediates deriving from zanthosimuline. Following the same synthetic strategy, we then prepared 14 new analogues. In this work, we identified two promising molecules with good activities against intramacrophage L. infantum amastigotes without any cytotoxicity. We also showed that slight changes in amide functional groups affect drastically their anti-parasitic activity.