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Ziziphus jujuba plant belongs to Rhamnaceous family and grows mainly in Europe, southern and eastern Asia, and Australia. Recent phytochemical investigation of plants provided some information on their biological effects, such as the hepatoprotective, immunostimulating, anti-obesity, anti-inflammatory, and anti-cancer properties. The current study investigated 34 phytocompounds from Z. jujuba and three anti-cancer drugs against three lung cancer target proteins. Drug likeliness screening revealed that two compounds dodecanoic acid and 7,9-di-tert-butyl-1-oxaspiro[4,5]deca-6,9-diene-2,8-dione possess zero violation, and compound azelaic acid possesses single violation against five drug rules. Molecular docking study reveals that 34 phytocompounds from Z. jujuba and three anti-cancer drugs showed docking score values in the range of −3.9 to −10.2 kcal/mol and −7.2 to −9.0 kcal/mol against three significant lung cancer target proteins. Furthermore, in silico screening top scored three phytocompounds campesterol, stigmast-5-en-3-ol, 7,9-di-tert-butyl-1-oxaspiro[4,5]deca-6,9-diene-2,8-dione and three anti-cancer drugs etoposide, paclitaxel, and doxorubicin utilized. Pharmacokinetic profile of three phytocompounds from Z. jujuba showed excellent absorption, distribution, metabolism, excretion, and toxicity profile than standard drugs. Furthermore, bioactivity and density functional theory analysis showed that phytocompounds from Z. jujuba possess better bioactivity scores and molecular electrostatic potentials than standard drugs. Molecular dynamics simulation results revealed that campesterol with CDK2 (PDB ID 1GII) and MDM2/P53 (4HFZ) target proteins possess better simulation trajectories and binding affinity than standard drugs. Further clinical trials of compounds (campesterol, stigmast-5-en-3-ol, 7,9-di-tert-butyl-1-oxaspiro[4,5]deca-6,9-diene-2,8-dione) are needed to check clinical pertinence toward lung cancer target proteins to commercialize these novel drug molecule in the drug industry. [ABSTRACT FROM AUTHOR]

The present study is to identify polycyclic aromatic bioactive phytocompounds from Eclipta alba against breast cancer target protein through in silico approach. Among 52 phytocompounds ecliptalbine, wedelolactone, ursolic acid and beta amyrin they have exhibited strong binding affinity against all three screened breast cancer target proteins such as matrix metallo protein (PDB ID 1RM8), estrogen receptor (PDB ID 3ERT) and progesterone receptor (PDB ID 4OAR). In drug likeliness 11 phytocompounds showed zero violations against all five drug likeliness rule, whereas all three anticancer drugs showed three minimal violations against the drug likeliness rule. Docking score of all screened compounds lies in the range of −4.3 Kcal/mol to −9.4 Kcal/mol in that ecliptalbine and ursolic acid show maximal binding affinity with all screened target proteins of breast cancer. Phytocompound ecliptalbine, wedelolactone and ursolic acid has shown excellent simulation trajectories with two screened target proteins in MDS analysis. Further compound ecliptalbine shown good phracokinetic and DFT scores which affirm that reason behind the good binding affinity with breast cancer target proteins. MMGBSA analysis also affirms the excellent binding affinity of ecliptalbine with breast cancer target proteins (–51.42 and −72.74 Kcal/mol) than the standard drug score. Finally ethanolic leaf extract of Eclipta alba showed excellent In vitro antioxidant (DPPH-IC50 83.40 µg/ml and ABTS–IC50 48.80 µg/ml) and cytotoxic potential (IC50 97.20 µg/ml) against triple-negative breast cancer cells (MDA-MB-231). Further these drug candidates can be validated through in vitro and preclinical studies to discover novel drug for breast cancer therapeutics. [ABSTRACT FROM AUTHOR]

In this study, in silico SARS-CoV-2 inhibitory potential of 19 marine algal polycyclic aromatic compounds plus three commercial anti-viral drug were validated comparatively against three target proteins. Among 19 marine algal compounds apigenin-7-O-neohesperidoside,dieckol, luteolin-7-rutinoside, oxoglyantrypine, hydroxypentafuhalol A, and pseudopentafuhalol B exhibited good binding affinity of toward all three screened targets (Mpro, RdRp, and spike protein) of SARS-CoV-2 shortlisted for further In silico virtual screening analysis. Complete docking interaction analysis indicates that apigenin-7-O-neohesperidoside, dieckol, luteolin-7-rutinoside compounds display very excellent binding and inhibitory potential against the all three screened targets of SAR-CoV-2 among 19 screened marine algal compounds than standard anti-viral drugs. DFT analysis affirms the essential Homo-Lumo orbital energies of apigenin-7-O-neohesperidoside to inhibit targets of SARS-CoV-2. Further in silico analysis confirmed three chosen marine algal compounds are showing their excellent pharmacokinetic and molecular electrostatic potentials (MEPs) toward targets of SARS-CoV-2. MD simulation analysis of three chosen marine algal compounds possesses best simulation trajectories toward the binding pocket of target proteins essential to inhibit SARS-CoV-2 multiplication comparatively standard anti-viral drugs possess lesser binding affinity. However, further human clinical trials are necessary to justify their clinical pertinence. [ABSTRACT FROM AUTHOR]

In the present study, in silico PLpro inhibitory potential of 28 polyphenolic compounds was validated, which possesses in vivo inhibitory potential against different SARS-CoV-2 replication enzymes. Among 28 polyphenolic compounds amentoflavone, tiliroside, papyriflavanol A and indinavir exhibited good binding affinity of toward PLpro has been considered for further virtual screening processes. Comprehensive analysis indicates that amentoflavone, tiliroside, and papyriflavanol A phenolic compounds demonstrate very high stability and higher inhibiting potential to bind with the Thr158 and Leu162 dyad of PLpro among 28 phenolic compounds. Further ADME and DFT analysis of amentoflavone, and papyrifalvanol A reveal that possess excellent pharmacokinetic and molecular electrostatic potentials. MD simulation and MM-GBSA analysis of amentoflavone, tiliroside, and one anti-viral drug indinavir toward PLpro (PDB ID 6W9C) result revealed that phenolic compounds amentoflavone, tiliroside possess excellent simulation trajectories toward the binding pocket of PLpro essential to inhibit SARS-CoV-2 multiplication. Further MM-GBSA analysis affirm that PLpro-amentoflavone complex exhibit high MMGBSA score of −106.56Kcal/mol. However, further human clinical trials are essential to justify their clinical pertinence. [ABSTRACT FROM AUTHOR]