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A series of 11 indole-based chalcones (IC1-11) with various electron donating and withdrawing groups at the para position of the phenyl ring B were synthesized. All the compounds were tested for their human monoamine oxidase (hMAO)-A and hMAO-B inhibitory potencies. Most of the synthesized candidates proved to be potent and selective inhibitors of MAO-B rather than MAO-A, with a reversible and competitive mode. Among them, compound IC9 was found to be a potent inhibitor of hMAO-B with Ki  = 0.01 ± 0.005 μM and a selectivity index of 120. It was found to be better than the standard drug, selegiline (hMAO-B with Ki  = 0.20 ± 0.020 μM) with a selectivity index of 30.55. PAMPA assays were carried out for all the compounds in order to evaluate the capacity of the compounds to cross the blood-brain barrier. Moreover, the most potent MAO-B inhibitor, IC9, was nontoxic at 5 and 25 μM, with 95.20 and 69.17% viable cells, respectively. The lead compound IC9 has an antioxidant property of 1.18 Trolox equivalents by ABTS assay. Molecular modeling studies were performed against hMAO-B to observe binding site interactions of the lead compound.

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Astragalin was isolated for the first time along with (-)hinokinin, aristolactam I and aristolochic acids (I & II) from the extracts of Aristolochia indica L. using a new, efficient preparative HPLC method. A reversed-phase HPLC method of analysis was developed to analyse the isolated compounds. The crude extracts and the isolated compounds were tested for their anti-inflammatory potential. We report here for the first time the anti-inflammatory effects of (-)hinokinin and aristolactam I against IL-6 (IC50 = 20.5 ± 0.5 and 52 ± 8 μM) and TNFα (IC50 = 77.5 ± 27.5 and 116.8 ± 83.25 μM), respectively. (-)Hinokinin exerted its anti-inflammatory effects via NFκB-dependent mechanism whereas aristolactam I may be effective via a mechanism independent of NFκB.

A hybrid pharmacophore approach is used to design and synthesize novel chalcone-thiazole hybrid molecules. Herein, thiazole has been hybridized with chalcone to obtain a new class of 5-LOX inhibitors. In vitro biological evaluation showed that most of the compounds were better 5-LOX inhibitors than the positive control, Zileuton (IC 50 = 1.05 ± 0.03 μM). The best compounds in the series, namely, 4k, 4n, and 4v (4k: IC 50 = 0.07 ± 0.02 μM, 4n: IC 50 = 0.08 ± 0.05 μM, 4v: 0.12 ± 0.04 μM) are found to be 10 times more active than previously reported 2-amino thiazole (2m: IC 50 = 0.9 ± 0.1 μM) by us. Further, 4k has redox (noncompetitive) while 4n and 4v act through a competitive inhibition mechanism. SAR indicated that the presence of methoxy/methyl either in the vicinity of chalcone or both thiazole and chalcone contributed to the synergistic inhibitory effect.