Azafluorene derivatives as inhibitors of SARS CoV-2 RdRp: Synthesis, physicochemical, quantum chemical, modeling and molecular docking analysis.

The crystal structures of 2-(1H-indol-3-yl)-4-phenyl-5H-indeno [( Cheng et al., 2007; Lee et al., 2003) 1,21,2-b]pyridine-3-carbonitrile (Ia) and 2-(1H-indol-3-yl)-4-(4-methoxyphenyl)-5H-indeno [( Cheng et al., 2007; Lee et al., 2003) 1,21,2-b]pyridine-3-carbonitrile (Ib) were determined using single crystal X-ray diffraction. Both the compounds belong to the triclinic system with the P-1 space group. The azafluorene ring system in both the compounds is effectively planar. The intermolecular interactions present in the compounds are discussed using Hirshfeld surface analysis, QTAIM and NCI. Compound Ib formed a strong interaction (-24.174 kJ/mol) with the solvent molecule. Both the compounds were geometry optimized using DFT/B3LYP level of theory. The compound's drug-like behaviors were studied using HOMO-LUMO analysis. The homology modeling of SARS CoV-2 RdRp was done utilizing the PDB 6NUR_A as a template. The model showed above 99% similarity with its preceder SARS CoV. The molecular docking analysis of the synthesized compounds was carried out along with some suggested drugs for COVID-19 and some phytochemicals. The docking results were then analyzed. The binding free energy of the complexes were calculated using MM-PB(GB)SA and ADMET properties of Ia and Ib were also predicted. Some suggestions are given from this analysis.

Crystal structure of 7'-(4-chloro-phen-yl)-2''-(4-meth-oxy-phen-yl)-7',7a',7'',8''-tetra-hydro-1'H,3'H,5''H-di-spiro-[indoline-3,5'-pyrrolo-[1,2-c]thia-zole-6',6''-quinoline]-2,5''-dione and an unknown solvent.

The asymmetric unit of the title compound, C34H28ClN3O3S, contains two independent mol-ecules (A and B). They differ essentially in the orientation of the 4-meth-oxy-phenyl ring with respect to the pyridine ring of the quinoline moiety; this dihedral angle is 37.01 (18)° in mol-ecule A but only 7.06 (17)° in mol-ecule B. In both mol-ecules, the cyclo-hexa-none ring of the iso-quinoline unit has a half-chair conformation. In the pyrrolo-thia-zole ring system, the pyrrolo ring in mol-ecule A has a twisted conformation on the N-C fused bond and an envelope conformation in mol-ecule B with the N atom as the flap. The thia-zole rings of both mol-ecules have twisted conformations on the N-C fused bond. In the crystal, the A mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers with an R 2 2(8) ring motif. These dimers are linked to the B mol-ecules by an N-H⋯N hydrogen bond and a series of C-H⋯O hydrogen bonds, forming layers lying parallel to the (101) plane. The layers are linked by C-H⋯π inter-actions and offset π-π inter-actions [inter-centroid distance = 3.427 (1) Å], forming a supra-molecular framework. The contribution to the scattering from a region of highly disordered solvent mol-ecules was removed with the SQUEEZE routine in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9-18]. The solvent formula mass and unit-cell characteristics were not taken into account during refinement.

3-[2-Cyclo-propyl-1-(2-fluoro-phen-yl)-2-oxoeth-yl]-5-(4-methyl-sulfanyl-benzyl-idene)-1,3-thia-zolidine-2,4-dione.

In the title compound, C(22)H(18)FNO(3)S(2), the five-membered thia-zolidine ring is planar (r.m.s. deviation = 0.003 Å) and forms dihedral angles of 70.2 (3), 73.16 (17) and 10.32 (14)° with the cyclo-propane, fluoro-benzene and methyl-thio-benzene rings, respectively. The sum of the bond angles around the thia-zolidine ring N atom (359.6°) indicates sp(2) hybridization. The mol-ecular structure features intra-molecular C-H⋯S, C-H⋯F and C-H⋯O inter-actions. In the crystal, no significant inter-molecular contacts were apparent.

[Cytotoxic compounds from the marine actinobacterium].

We isolated a bioactive streptomycete from marine sediment samples collected at Bay of Bengal, India, during our systematic study of marine actinobacteria. The taxonomic studies indicated that the isolate is related to Strepomyces corchorusii. However, it differed in certain aspects, and, hence, was designated as S. corchorusii AUBN(1)/7. A solvent extraction followed by a chromatographic purification helped obtain from the isolate two cytotoxic compounds, which were identified as resistomycin, a quinone-related antibiotic, and tetracenomycin D, an anthraquinone antibiotic, on the basis of spectral data of pure compounds. They demonstrated in vitro a potent cytotoxic activity against cell lines HMO2 (gastric adenocarcinoma) and HepG2 (hepatic carcinoma) and also exhibited weak antibacterial activities against Gram-positive and Gram-negative bacteria. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.