Synthesis, E-pharmacophore, Molecular Docking Studies with SARS-CoV-2 Protease, Their Biological Properties and DFT Calculation of Some New Indolo[3,2-c]Isoquinoiline Hybrids

A series of novel indolo[3,2-c]isoquinoline hybrids derivatives were synthesized. On the basis of spectroscopic and analytical data, the structures of newly synthesized compounds were determined. They were further evaluated for their in vitro antimicrobial, antioxidant anticancer and anti-TB activities. Results reveal that compounds 4a and 5a displayed better potency against all bacterial strains and compound 3b showed significant antifungal action against all fungi tested. Compound 4b display excellent antioxidant capability. Compounds 3a, 4a, and 5a bearing chloro on indolo[3,2-c]isoquinoline ring were found have higher potency against all cancer cell lines. Compound 5b displayed potent antitubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC 0.12 μg/mL. Consequently, a five-point e-pharmacophore model (AADDR) was built. Docking studies displayed that compounds 2a, 2b, 3a, 4b, and 4c exhibited stronger interactions and higher binding affinity toward Glu166, Gln189, and His41, which are critical amino acid residues that play a significant role in PDB: 7D1M (SARS-CoV-2 Mpro) through hydrogen bonding, hydrophobic and π-π interactions. Further, frontier molecular orbitals studies were executed to understand their orbital energies and HOMO-LUMO lowest energy gap is 8.39 eV shown by compound 5a.

Synthesis of novel indolo[3,2-c]isoquinoline derivatives bearing pyrimidine, piperazine rings and their biological evaluation and docking studies against COVID-19 virus main protease.

A series of hybrid indolo[3,2-c]isoquinoline (δ-carboline) analogs incorporating two pyrimidine and piperizine ring frameworks were synthesized. Intending biological activities and SAR we propose replacements of fluorine, methyl and methoxy of synthetic compounds for noteworthy antimicrobial, antioxidant, anticancer and anti-tuberculosis activities. Among these compounds 3a, 4a and 5e were progressively strong against E. coli and K. pneumonia. Whereas, compounds 4a, 5a and 6a with addition of various functional groups (OCH3, CH3) were excellent against S. aureus and B. subtilis. Compound 5c exhibited strong RSA and dynamic ferrous ion (Fe2+) metal chelating impact with IC50 of 7.88 ± 0.93 and 4.06 ± 0.31 µg/mL, respectively. Compound 5e was considerably cytotoxic against all cancer cells displaying activity better than the standard drug. Compounds 6b and 6e inhibited M. tuberculosis (MIC 1.0 mg/L) considerably. Molecular docking studies indicate that compounds 4d, 5a, 5b, 6b and 6f exhibited good interactions with 6LZE (COVID-19) and 6XFN (SARS-CoV-2) at active sites. The structure of the synthesized compounds were elementally analyzed using IR, 1H, 13C NMR and mass spectral information.

Novel indolo [3,2-c]isoquinoline-5-one-6-yl [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazole analogues: Design, synthesis, anticancer activity, docking with SARS-CoV-2 Omicron protease and MESP/TD-DFT approaches.

Indoloisoquinoline derivatives are associated with varieties of biological and pharmacological properties. Therefore, we herein reported the synthesis of novel series of indolo [3,2-c]isoquinoline incorporated with [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazole moieties. Spectroscopic methods were used to determine the chemical structures of these molecules. Whereas, the B3LYP functional with the def2-SVP basis set were used to improve TD-DFT geometries and solvent effects. Investigations, which are directly connected to the optical spectra (absorption and emission) of molecules. These findings reveals that the compound 3d-f with a strong electron acceptor NO2 exhibited UV-visible spectra peaks to near infrared (NIR) range in solvents. Compound 3e exhibited a lowest ∆E of 2.28 eV in MeCN. Further, among the newly synthesized compounds 3d and 3g exhibits highest activity against four cell lines with strongest potent cytotoxicity, as contrasted to the control drug (Doxorubicin). Docking experiments revealed that compounds in contrast to 3a and 3d had strong interactions with Asn322, Met323, Ala387,Ala386, Gln506 and Gly326 with a greater binding affinity which are important amino acid residues that play a key role in SARS-CoV-2 Omicron main protease (Mpro) through hydrophobic, hydrogen bonding, Pi-sigma, Pi-sulfur and van der Waals interactions.

Synthesis, E-pharmacophore, Molecular Docking Studies with SARS-CoV-2 Protease, Their Biological Properties and DFT Calculation of Some New Indolo[3,2-c]Isoquinoiline Hybrids

A series of novel indolo[3,2-c]isoquinoline hybrids derivatives were synthesized. On the basis of spectroscopic and analytical data, the structures of newly synthesized compounds were determined. They were further evaluated for their in vitro antimicrobial, antioxidant anticancer and anti-TB activities. Results reveal that compounds 4a and 5a displayed better potency against all bacterial strains and compound 3b showed significant antifungal action against all fungi tested. Compound 4b display excellent antioxidant capability. Compounds 3a, 4a, and 5a bearing chloro on indolo[3,2-c]isoquinoline ring were found have higher potency against all cancer cell lines. Compound 5b displayed potent antitubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC 0.12 μg/mL. Consequently, a five-point e-pharmacophore model (AADDR) was built. Docking studies displayed that compounds 2a, 2b, 3a, 4b, and 4c exhibited stronger interactions and higher binding affinity toward Glu166, Gln189, and His41, which are critical amino acid residues that play a significant role in PDB: 7D1M (SARS-CoV-2 Mpro) through hydrogen bonding, hydrophobic and π-π interactions. Further, frontier molecular orbitals studies were executed to understand their orbital energies and HOMO-LUMO lowest energy gap is 8.39 eV shown by compound 5a.