Virtual Combinatorial Chemistry and Pharmacological Screening: A Short Guide to Drug Design

Abstract

Traditionally, drug development involved the individual synthesis and biological evaluation of hundreds to thousands of compounds with the intention of highlighting their biological activity, selectivity, and bioavailability, as well as their low toxicity. On average, this process of new drug development involved, in addition to high economic costs, a period of several years before hopefully finding a drug with suitable characteristics to drive its commercialization. Therefore, the chemical synthesis of new compounds became the limiting step in the process of searching for or optimizing leads for new drug development. This need for large chemical libraries led to the birth of high-throughput synthesis methods and combinatorial chemistry. Virtual combinatorial chemistry is based on the same principle as real chemistry—many different compounds can be generated from a few building blocks at once. The difference lies in its speed, as millions of compounds can be produced in a few seconds. On the other hand, many virtual screening methods, such as QSAR (Quantitative Sturcture-Activity Relationship), pharmacophore models, and molecular docking, have been developed to study these libraries. These models allow for the selection of molecules to be synthesized and tested with a high probability of success. The virtual combinatorial chemistry–virtual screening tandem has become a fundamental tool in the process of searching for and developing a drug, as it allows the process to be accelerated with extraordinary economic savings.

Re-envisioning the Design of Nanomedicines: Harnessing Automation and Artificial Intelligence

“…Similar problems have been overcome in drug discovery using quantitative structure-activity relationships (QSAR). These empirical models are used to find statistical correlations between chemical structure and receptor activity [62,63]. Increasingly, traditional QSAR models with ML algorithms are being used to improve data processing [64][65][66][67].…”

One-Pot Multicomponent Polymerization, Metal-, and Non-Metal-Catalyzed Synthesis of Organoselenium Compounds

“…The latter has emerged as a robust tool in medicinal chemistry [ 44 , 45 ]. It is now widely and consecutive covalent bonds formed between different building blocks [ 46 ]. Concurrently, drug candidates are discovered and selected by the screening of small molecule libraries for particular biological targets [ 47 ].…”

Synthesis, spectral characterization, crystal structure and computational investigation of 2-formyl-6-methoxy-3-carbethoxy quinoline as potential SARS-CoV inhibitor

“…In vitro studies showed that it can controlSARS-CoV-2 infections effectively with significant reduction in mortality [ 14 ]. Umifenovir, Favipiravir, Molnupiravir [ 15 ], Nirmatrevir mixed with Ritonavi [ 16 ], Ribavirin [ 17 ]and Interferon are some of the other antiviral agents approved for treatment of SARS-CoV-2 [ 18 ], while some of them might have potential side effects [ 19 ]. COVID-19 pandemic has put the global research on a war footing to find an effective drugas well as suitableantiviral therapies [ 20 ].…”

“…Synthetic organic chemistry provides newer routes of drug development with new molecules for further investigations [ 21 ]. The new drugs with required pharmacological quality can be crafted carefully following a step by step synthetic procedures [ 15 ].…”