Anti-Cancer Potential of Phytocompounds from Ziziphus jujuba against Lung Cancer Target Proteins: An In Silico Validation

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.