Bauhinoxepins A and B: New Antimycobacterial Dibenzo[b,f]oxepins from Bauhinia saccocalyx

Two new antimycobacterial dibenzo[b,f]oxepins, bauhinoxepins A (=3,3,5‐trimethylbenzo[b]pyrano[g][1]benzoxepin‐6,11‐diol; 1 ) and B (=6‐methoxy‐7‐methyl‐2‐(3‐methylbut‐2‐enyl)dibenzo[b,f]oxepine‐1,8‐diol; 2 ), were isolated from the roots of Bauhinia saccocalyx, and their structures were elucidated by analysis of spectroscopic data. Bauhinoxepins A and B exhibited antimycobacterial activities with respective minimum‐inhibitory concentrations (MIC) of 6.25 and 12.5 μg/ml. They were inactive (at 20 μg/ml) against the malarial parasite, and also inactive (at 20 μg/ml) towards the Vero, KB, and BC cell lines.     

Water‐Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4‐Oxadiazoles

Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However, the present work revealed that water‐assisted generation of nitrile oxides proceeds under mild acidic conditions (pH 4–5). Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts, thus yielding isoxazoles and isoxazolines, respectively, with excellent stereoselectivity toward five‐ and six‐membered cyclic alkenes. A double stereoselective cycloaddition of two units of a nitrile oxide with cyclohexene was also achieved, thus yielding 1,2,4‐oxadiazole derivatives having a unique hybrid isoxazoline‐oxadiazole skeleton. Enantiomerically pure isoxazolines were prepared from monoterpenes with a ring strain. In one case, the isoxazoline with a butterfly‐like structure was simply prepared, and it might be used as a ligand in asymmetric catalysis.     

Atropisomeric myristinins: selective COX-2 inhibitors and antifungal agents from Myristica cinnamomea

The first naturally occurring atropisomeric flavans, myristinins B (2), C (2a), E (4), and F (4a), together with their corresponding trans-isomers, myristinins A (1) and D (3), were isolated from the CH(2)Cl(2) extract of Myristica cinnamomea fruits. Compounds 1, the mixture of 2 and 2a, and the mixture of 4 and 4a, exhibited antifungal activity against Candida albicans with IC(50) values ranging from 5.9 to 8.8 microg/mL, and they selectively inhibited the enzyme cyclooxygenase-2 (COX-2).     

In silico study directed towards identification of the key structural features of GyrB inhibitors targeting MTB DNA gyrase: HQSAR,CoMSIA and molecular dynamics simulations

ABSTRACT

Mycobacterium tuberculosis DNA gyrase subunit B (GyrB) has been identified as a promising target for rational drug design against fluoroquinolone drug-resistant tuberculosis. In this study, we attempted to identify the key structural feature for highly potent GyrB inhibitors through 2D-QSAR using HQSAR, 3D-QSAR using CoMSIA and molecular dynamics (MD) simulations approaches on a series of thiazole urea core derivatives. The best HQSAR and CoMSIA models based on IC₅₀ and MIC displayed the structural basis required for good activity against both GyrB enzyme and mycobacterial cell. MD simulations and binding free energy analysis using MM-GBSA and waterswap calculations revealed that the urea core of inhibitors has the strongest interaction with Asp79 via hydrogen bond interactions. In addition, cation-pi interaction and hydrophobic interactions of the R₂ substituent with Arg82 and Arg141 help to enhance the binding affinity in the GyrB ATPase binding site. Thus, the present study provides crucial structural features and a structural concept for rational design of novel DNA gyrase inhibitors with improved biological activities against both enzyme and mycobacterial cell, and with good pharmacokinetic properties and drug safety profiles.     

A novel tricyclic polyketide and its biosynthetic precursor azaphilone derivatives from the endophytic fungus Dothideomycete sp

Azaphilone derivatives 1 and 2 and a novel tricyclic polyketide 3, together with a known azaphilone, austdiol (4), were isolated from the endophytic fungus Dothideomycete sp., which was isolated from a Thai medicinal plant, Tiliacora triandra. Compound 3 is the first polyketide having a tricyclic 6,6,6 ring system, which is similar to that of a terpenoid skeleton. The absolute configurations of stereogenic centers in 1-3 were addressed by Mosher's method and biosynthetic analogy with a known azaphilone isolated from the same fungus. Cytotoxic and antimicrobial activities of the isolated compounds were evaluated.     

A new 22,26-seco physalin steroid from Physalis angulata

Abstract

A new 22,26-seco physalin, physalin XI (1) together with 5 known compounds, were isolated from the dichloromethane extract of Physalis angulata L. The structure of isolated compounds was elucidated by spectroscopic analysis. The effects of isolated compounds on in vitro cytotoxicity were investigated. Compound 1 was assessed for its cytotoxicity against cancer cell lines (HepG2, HeLa, HuCCA-1, T47-D and A-549) and a normal cell line (MRC-5), and the result showed that it has no activity. Compounds 2 and 4 are highly toxic to H69AR and MDA-MB-23 cell lines. This property appears to be related to the presence of their conjugated double bond or epoxy groups and is a more reliable indication of toxicity than substitution on C(5)–C(6).