Identification of novel bioactive molecules from garlic bulbs: A special effort to determine the anticancer potential against lung cancer with targeted drugs

Abstract

Garlic ( Allium sativum L.), is a predominant spice, which is used as an herbal medicine and flavoring agent, since ancient times. It has a rich source of various secondary metabolites such as flavonoids, terpenoids and alkaloids, which have various pharmacological properties. Garlic is used in the treatment of various ailments such as cancer, diabetes and cardiovascular diseases. The present study aims to explore the plausible mechanisms of the selected phytocompounds as potential inhibitors against the known drug targets of non-small-cell lung cancer (NSCLC). The phytocompounds of garlic were identified by gas chromatography-mass spectrometry (GC–MS) technique. Subsequently, the identified phytocompounds were subjected to molecular docking to predict the binding with the drug targets, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and group IIa secretory phospholipase A2 (sPLA2-IIA). Molecular dynamics is used to predict the stability of the identified phytocompounds against NSCLC drug targets by refining the intermolecular interactions formed between them. Among the 12 phytocompounds of garlic, three compounds[1,4-dimethyl-7-(1-methylethyl)-2-azulenyl]phenylmethanone, 2,4-bis(1-phenylethyl)-phenol and 4,5–2 h-oxazole-5-one,4-[3,5-di-t-butyl-4-methoxyphenyl] methylene-2-phenyl were identified as potential inhibitors, which might be suitable for targeting the different clinical forms of EGFR and dual inhibition of the studied drug targets to combat NSCLC. The result of this study suggest that these identified phytocompounds from garlic would serve as promising leads for the development of lead molecules to design new multi-targeting drugs to address the different clinical forms of NSCLC.

In Silico Approach to Search Various Phytochemicals as Potential Therapeutics Against the Spike Protein from Alpha Variant Strain (B.1.1.7) of SARS-CoV-2

“…Hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin displayed lower binding free energies towards 7DDN protein of SARS-CoV-2, according to findings of this study. These compounds have the ability to act as antiviral phytochemicals, preventing the virus from replicating (Padmini et al, 2020;Li et al, 2020;Khare et al, 2020). These results constitute merely a preliminary examination to aid later tests, which will begin in animal models or human clinical trials.…”

“…Intermolecular interaction involves hydrophobic, dispersion, or Van der Waals forces, H bonding, and electrostatic forces (Padmini et al, 2020). Hydrophobic interactions seem to be the dominating power for binding, whereas hydrogen bonding and electrostatic interactions likely to influence the precision of the complexation (Nag et al, 2021).…”

“…Many therapeutic vegetation includes alkaloids, which are bitter-tasting compounds which have been found worldwide yet often hazardous (Kushwaha et al, 2021;Seema et al, 2020). Glycosides comprise potent medications pharmacologically active such as foxglove as well as lily of the hill (Padmini et al, 2020). Medications comprise digoxin but also digitoxin, which together help the heart rhythm thus function effective antihypertensive (Azim et al, 2020).…”

Bio-Inspired Fabrication of Silver Nanoparticles Using High Altitude Squamulose Lichen Extract and Evaluation of its Antioxidant, Anticandida and Cytotoxic properties

“…Structure of chemical compounds identi ed using GC-MS analysis were obtained from the Pubchem database and the three-dimensional protein structure of EGFR protein involved in lung cancer pathogenesis was downloaded from RCSCB protein data bank (PDB) [42]. The Graphical User Interface program "AutoDock Tools" was used to prepare, run, and analyze the docking simulations.…”

Combined in vitro and in silico approach to evaluate the inhibitory potential of an underutilized allium vegetable and its pharmacologically active compounds on multidrug resistant Candida species

“…A. cepa and A. sativum are potential antimicrobial agents and a recent study reports that Silver nanoparticles synthesized from these species have shown to exert antimicrobial activity against vaginal pathogens Streptococcus pneumoniae and Pseudomonas aeruginosa ( Bouqellah et al, 2018 ). Novel bioactive metabolites from A. sativum have been recently identified as potent anti-cancer drug targets ( Padmini et al, 2020 ). Numerous other vegetables under the Allium genus have significant medicinal values but still remain unrecognized and underutilized.…”