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Boswellic acids (BAs) have been shown to possess antiviral activity. Using bioinformatic methods, it was tested whether or not acetyl‐11‐keto‐β‐boswellic acid (AKBA), 11‐keto‐β‐boswellic acid (KBA), β‐boswellic acid (BBA), and the phosphorylated active metabolite of Remdesivir® (RGS‐P3) bind to functional proteins of SARS‐CoV‐2, that is, the replicase polyprotein P0DTD1, the spike glycoprotein P0DTC2, and the nucleoprotein P0DTC9. Using P0DTD1, AKBA and KBA showed micromolar binding affinity to the RNA‐dependent RNA polymerase (RdRp) and to the main proteinase complex Mpro. Phosphorylated BAs even bond in the nanomolar range. Due to their positive and negative charges, BAs and RGS‐P3 bond to corresponding negative and positive areas of the protein. BAs and RGS‐P3 docked in the tunnel‐like cavity of RdRp. BAs also docked into the elongated surface rim of viral Mpro. In both cases, binding occurred with active site amino acids in the lower micromolecular to upper nanomolar range. KBA, BBA, and RGS‐P3 also bond to P0DTC2 and P0DTC9. The binding energies for BAs were in the range of −5.8 to −6.3 kcal/mol. RGS‐P3 and BAs occluded the centrally located pore of the donut‐like protein structure of P0DTC9 and, in the case of P0DTC2, RGS‐P3 and BAs impacted the double‐wing‐like protein structure. The data of this bioinformatics study clearly show that BAs bind to three functional proteins of the SARS‐CoV‐2 virus responsible for adhesion and replication, as does RGS‐P3, a drug on the market to treat this disease. The binding effectiveness of BAs can be increased through phosphate esterification. Whether or not BAs are druggable against the SARS‐CoV‐2 disease remains to be established., Bioinformatic methods showed that acetyl‐11‐keto‐β‐boswellic acid, 11‐keto‐β‐boswellic acid, β‐boswellic acid, and the phosphorylated active metabolite of Remdesivir® bind to functional proteins of SARS‐CoV‐2: the replicase polyprotein P0DTD1, the spike glycoprotein P0DTC2, and the nucleoprotein P0DTC9. The binding effectiveness of the boswellic acids can be increased through phosphate esterification.

The direct aldol reaction between acetone and 4-nitrobenzaldehyde catalyzed by sterically hindered l-prolinamide derivative (64 atoms) of the (11S,12S)-9,10-dihydro-9,10-ethanoanthracene-11,12-diamine molecule has been investigated using density functional theory at the B3LYP/6-31G(d) level of theory. The reliability of the B3LYP/6-31G(d) calculations to elucidate the reaction mechanism and estimate activation and reaction energies was confirmed by energy calculation of the net reaction with full geometry optimizations of the reactants and product at the B3LYP/6-311++G(2d,2p) as well as B2PLYP/def2-TZVPP levels with correction to Van der Waals interaction. The calculations reveal that the l-prolinamide derivative catalyzes the reaction according to a multistep enamine mechanism with highly activated C–C bond and/or enamine formation in the proposed mechanism. The final elementary reaction – the C–N bond cleavage in the chiral diol adduct – is accompanied by a very large barrier, which may inhibit further progression of the reaction. The origin of the enantioselectivity and the corresponding reaction paths to a chiral product were unambiguously identified. Copyright © 2012 John Wiley & Sons, Ltd.

Scaffold diversity analysis of compound databases has multiple applications in medicinal chemistry and drug discovery including library design, compounds acquisition, virtual screening and assessment of structure-activity-relationships. The scaffold diversity is commonly measured based on frequency counts. Further information can be obtained by considering the specific distribution of the molecules in those scaffolds. To this end, we introduce in this work the use of an entropy-based information metric to assess the scaffold diversity of compound data sets. As a test case we analyzed the scaffold diversity of 16 data sets of active compounds comparable in size targeting five protein classes of interest in drug design. The diversity was also assessed in terms of frequency counts and scaffold retrieval curves. The entropy-based information metric takes into account the frequency distribution of the different scaffolds and is a complementary measure of scaffold diversity enabling a more comprehensive analysis.

The continuing rise in tuberculosis incidence and the problem of drug resistance strains have prompted the research on new drug candidates and the mechanism of drug resistance. Molecular docking and molecular dynamics simulation (MD) were performed to study the binding of isoniazid onto the active site of Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA) in an attempt to address the mycobacterial resistance against isoniazid. Results show that isonicotinic acyl-NADH (INADH) has an extremely high binding affinity toward the wild type InhA by forming stronger interactions compared to the parent drug (isoniazid) (INH). Due to the increase of hydrophobicity and reduction in the side chain’s volume of A94 of mutant type InhA, both INADH and the mutated protein become more mobile. Due to this reason, the molecular interactions of INADH with mutant type are weaker than that observed with the wild type. However, the reduced interaction caused by the fluctuation of INADH and the mutant protein...