Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents

Abstract

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher’s opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.

Constituents, Antibacterial Adhesion, Cytotoxic and in Vitro Metastasis Blocking Properties of Salvia fruticosa Essential Oils from Three Palestinian Localities

“…Numerous plant species have been used for centuries to treat and prevent infectious and non‐infectious diseases worldwide. Actually, various pharmaceutical dosage forms are now derived from crude plant extracts, plant EOs, or pure isolated pharmacological active compounds produced in the pharmaceutical industry [37] …”

“…Actually, various pharmaceutical dosage forms are now derived from crude plant extracts, plant EOs, or pure isolated pharmacological active compounds produced in the pharmaceutical industry. [37] Chemical Constituents of S. fruticosa…”

Plant-Derived Natural Products as Lead Agents against Common Respiratory Diseases

“…Therefore, future study should focus on the isolation and identification of non-/less toxic and more effective natural compounds through bioassay-guided isolation, high-throughput-screenings, metabolomics, molecular modelling, virtual screening, natural product libraries, and database mining [ 198 ], while elucidation of the mechanisms of action of bioactive compounds, lead optimization, toxicological considerations, product formulation, evaluation of pharmacokinetic parameters, dosage regimens, and targeted drug delivery will remain crucial in the discovery and development of respiratory drugs [ 77 , 199 ]. The development of new-age technologies such as the application of biogenetic metal-based nanoparticles in medicine (nanomedicine) is another giant stride, which so far has ensured successful drug delivery with the use of nebulizers that create a particle size capable of reaching the alveoli, for faster and more effective treatment at low therapeutic doses [ 200 , 201 ].…”

From Traditional Ethnopharmacology to Modern Natural Drug Discovery: A Methodology Discussion and Specific Examples

“…However, although computational chemistry has revolutionized the process of drug discovery, some limitations still exist, inherent to the accuracy of the computer programs used and the possible overfitting, induced by in silico methods, necessitating proper experimental validation. In recent years, innovative extraction technologies, including semi-bionic extraction; supercritical fluid extraction; microwave-assisted, ultrasonic-assisted, and enzyme-assisted extraction; molecular distillation methods; membrane separation technology; and sophisticated new methodologies and instrumentation such as HPLC-MS, LC-MS, GC-MS, NMR, and crystallography, in parallel with the development of biology and clinical and experimental medicine, have allowed the re-evaluation of the corpus of traditional knowledge, the determination of chemical components of plant extracts, the identification of "active compound(s)", and the development of novel drugs [12,13]. Galantamine [14], an Amaryllidaceae-type alkaloid from Galanthus woronowii Losinsk and other species of this genus, which has been recently approved for the treatment of early-onset Alzheimer's disease, is an example of a recent achievement.…”

“…Galantamine [14], an Amaryllidaceae-type alkaloid from Galanthus woronowii Losinsk and other species of this genus, which has been recently approved for the treatment of early-onset Alzheimer's disease, is an example of a recent achievement. A detailed presentation of plant-derived drug discovery in the last 30 years has been extensively reviewed and discussed in a recent series of publications [13,[15][16][17].…”