3-Benzylidene-4-chromanones: a novel cluster of anti-tubercular agents

Abstract

In a quest for developing novel anti-tubercular agents, a series of 3-benzylidene-4-chromanones 1a-l were evaluated for growth inhibition of Mycobacterium tuberculosis H 37 Rv. Three promising compounds 1d, g, j emerged as the lead compounds with the IC 50 and IC 90 values of less than 1 mg/mL. Evaluation of the potent compounds 1d, g, j and k against Vero monkey kidney cells revealed that these compounds are far more toxic to M. tuberculosis than to Vero cells. Structure-activity relationships demonstrated that 3-benzylidene-4-chromanones are more potent against M. tuberculosis than the related 2-benzylidene cycloalkanones and the meta substituted chromanone derivatives are more active than their ortho-and para-counterparts. Some guidelines for amplifying the project are presented.

Synthesis of Coumarin and Homoisoflavonoid Derivatives and Analogs: The Search for New Antifungal Agents

“…The homoisoflavonoids 21-24 were the next most active compounds, after compound 8. This class of natural products presents many biological properties, such as cytotoxic [49], antioxidant, anti-inflammatory [50], antibacterial [51], antiviral [52] and antifungal activity [53]. For the antifungal activity observed in this study, we evaluated the influence of the methoxyl substituent present in the B ring of derivatives 22, 23, and 24.…”

“…Our findings suggest that the presence of the methoxyl group at the meta position of the B ring contributed to the better antifungal bioactivity found for derivative 23. Das et al 2015 [51] evaluated analogues 22, 23, and 24, among other 3-benzylidene-4-chromanones derivatives, for anti-mycobacterial activity (Mycobacterium tuberculosis); to obtain potent anti-mycobacterial agents, the authors sug-gested the importance of inserting small substituent groups into the aromatic rings of the analog series under study. They also related the better bioactivity with the position of aromatic substituents in the B ring.…”

Benzopyran-Core as an Antimycobacterial Agent

“…Kuete et al [86] isolated 5 polyphenols from twigs of Dorstenia barteri and screened them for antimycobacterial activity against M. Smegmatis and Mtb H 37 Rv strains. Among the polyphenols, 4-hydroxylonchocarpin (46) exhibited pronounced antimycobacterial activity (MIC=9.76µg/ mL) against both mycobacterial strains.…”

“…The compounds 7(a-d) showed moderate antitubercular activity with MIC values ranging between 10 and 12 µg/mL (Figure 5). Das et al [46] reported the synthesis of 3-benzylidine-4-chromanones and evaluated them for growth inhibition of Mtb H 37 Rv in BACTEC 12B medium and the growth inhibition was determined by the broth dilution assay [47]. Compound (8a) with a meta-bromo substituent on the benzylidine moiety showed highest inhibition (99%) at a concentration of 10µg/mL (Figure 5).…”

Chemistry and Antifungal Activity of Homoisoflavonoids

“…Figure 3: Basic chemical structures of the diferent types of homoisofavonoids found in nature. [6]; cytotoxicity against human cancer cell lines [7,8]; antidiabetic activity [9]; and antimicrobial activity [10][11][12][13][14][15]; among others [16,17]. Each year, fungal infections afect more than a billion people worldwide, with candidiasis representing about 75% to 88% of these infections.…”