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From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential

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A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 50253

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Dr. Giovanni Ribaudo

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Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
Interests: medicinal chemistry; organic synthesis; analytical chemistry; mass spectrometry; NMR; natural products; molecular modeling
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Prof. Dr. Laura Orian

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Department of Chemical Sciences, University of Padova, Via Marzolo, 1, 35131 Padova, Italy
Interests: computational chemistry; physical chemistry; catalysis; molecular design
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

In the last two decades, computer-aided modeling has strongly supported scientists’ intuition to design functional molecules. High-throughput screening protocols, mainly based on classical mechanics atomistic potentials, are largely employed in biology and medicinal chemistry studies with the aim of simulating drug-likeness and bioactivity in terms of efficient binding to the target receptors. The advantages of this approach are short time outcomes, the possibility of repurposing commercially available drugs, consolidated protocols, and the availability of large databases. On the other hand, these studies do not intrinsically provide reactivity information, which requires quantum mechanical methodologies so far only applicable to significantly smaller and simplified systems. These latter studies focus on the drug itself, considering the chemical properties related to its structural features and motifs. The advantages consist of: (i) the rationalization of the drug activity in terms of its precise and quantitative mechanism, which is strictly related to its chemical structure; and (ii) the identification of key molecular motifs for the rational design of novel drugs or slight modifications of already approved drugs, finalized to their repurposing. These studies provide insights for better understanding the chemistry principles which rule the diseases at the molecular level, as well as the possible mechanisms for restoring the physiological equilibrium.

In this Special Issue, we intend to collect contributions (reviews and original research articles) dealing with successful stories of drug improvement or design by classic protocols, by quantum mechanical mechanistic investigation, or by hybrid approaches like QM/MM or QM/ML (machine learning). Lastly, we also aim to receive works in which the drug design has been performed without computer help, but in the lab with the help of chemical intuition and... serendipity! The common aspect that we stress is the recognition of chemical molecular motifs which are the key aspects for the drug potential. Topics of interest include but are not limited to the following:

- Antioxidants;

- Natural and semi-synthetic compounds;

- Natural supplements containing bioactive molecules;

- Improved bioactivity of known drugs;

- Drugs and drug-like compounds acting through multiple mechanisms of action.

Dr. Giovanni Ribaudo
Prof. Dr. Laura Orian
Guest Editors

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Published Papers (14 papers)

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Editorial

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3 pages, 189 KiB

Open AccessEditorial

From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential

by Giovanni Ribaudo and Laura Orian

Molecules 2022, 27(13), 4144; https://doi.org/10.3390/molecules27134144 - 28 Jun 2022

Viewed by 1407

Abstract

Health is a fundamental human right and is a global goal to which extensive research effort is devoted in all fields [...] Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

Research

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22 pages, 6211 KiB

Open AccessArticle

Seafood Paramyosins as Sources of Anti-Angiotensin-Converting-Enzyme and Anti-Dipeptidyl-Peptidase Peptides after Gastrointestinal Digestion: A Cheminformatic Investigation

by Tsun-Thai Chai, Clara Chia-Ci Wong, Mohamad Zulkeflee Sabri and Fai-Chu Wong

Molecules 2022, 27(12), 3864; https://doi.org/10.3390/molecules27123864 - 16 Jun 2022

Cited by 9 | Viewed by 2082

Abstract

Paramyosins, muscle proteins occurring exclusively in invertebrates, are abundant in seafoods. The potential of seafood paramyosins (SP) as sources of anti-angiotensin-converting-enzyme (ACE) and anti-dipeptidyl-peptidase (DPP-IV) peptides is underexplored. This in silico study investigated the release of anti-ACE and anti-DPP-IV peptides from SP after gastrointestinal (GI) digestion. We focused on SP of the common octopus, Humboldt squid, Japanese abalone, Japanese scallop, Mediterranean mussel, Pacific oyster, sea cucumber, and Whiteleg shrimp. SP protein sequences were digested on BIOPEP-UWM, followed by identification of known anti-ACE and anti-DPP-IV peptides liberated. Upon screening for high-GI-absorption, non-allergenicity, and non-toxicity, shortlisted peptides were analyzed via molecular docking and dynamic to elucidate mechanisms of interactions with ACE and DPP-IV. Potential novel anti-ACE and anti-DPP-IV peptides were predicted by SwissTargetPrediction. Physicochemical and pharmacokinetics of peptides were predicted with SwissADME. GI digestion liberated 2853 fragments from SP. This comprised 26 known anti-ACE and 53 anti-DPP-IV peptides exhibiting high-GI-absorption, non-allergenicity, and non-toxicity. SwissTargetPrediction predicted three putative anti-ACE (GIL, DL, AK) and one putative anti-DPP-IV (IAL) peptides. Molecular docking found most of the anti-ACE peptides may be non-competitive inhibitors, whereas all anti-DPP-IV peptides likely competitive inhibitors. Twenty-five nanoseconds molecular dynamics simulation suggests the stability of these screened peptides, including the three predicted anti-ACE and one predicted anti-DPP-IV peptides. Seven dipeptides resembling approved oral-bioavailable peptide drugs in physicochemical and pharmacokinetic properties were revealed: AY, CF, EF, TF, TY, VF, and VY. In conclusion, our study presented in silico evidence for SP being a promising source of bioavailable and safe anti-ACE and anti-DPP-IV peptides following GI digestions. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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19 pages, 4985 KiB

Open AccessArticle

Statistical Methods in the Study of Protein Binding and Its Relationship to Drug Bioavailability in Breast Milk

by Karolina Wanat and Elżbieta Brzezińska

Molecules 2022, 27(11), 3441; https://doi.org/10.3390/molecules27113441 - 26 May 2022

Cited by 1 | Viewed by 1548

Abstract

Protein binding (PB) is indicated as the factor most severely limiting distribution in the organism, reducing the bioavailability of the drug, but also minimizing the penetration of xenobiotics into the fetus or the body of a breastfed child. Therefore, PB is an important aspect to be analyzed and monitored in the design of new drug substances. In this paper, several statistical analyses have been introduced to find the relationship between protein binding and the amount of drug in breast milk and to select molecular descriptors responsible for both pharmacokinetic phenomena. Along with descriptors related to the physicochemical properties of drugs, chromatographic descriptors from TLC and HPLC experiments were also used. Both methods used modification of the stationary phase, using bovine serum albumin (BSA) in TLC and human serum albumin (HSA) in HPLC. The use of the chromatographic data in the protein binding study was found to be positive —the most effective application of normal-phase TLC and HPLC_HSA data was found. Statistical analyses also confirmed the prognostic value of affinity chromatography data and protein binding itself as the most important parameters in predicting drug excretion into breast milk. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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16 pages, 4295 KiB

Open AccessArticle

Anti-Inflammatory Potential of Fucoidan for Atherosclerosis: In Silico and In Vitro Studies in THP-1 Cells

by Etimad Huwait, Dalal A. Al-Saedi and Zeenat Mirza

Molecules 2022, 27(10), 3197; https://doi.org/10.3390/molecules27103197 - 17 May 2022

Cited by 13 | Viewed by 3713

Abstract

Several diseases, including atherosclerosis, are characterized by inflammation, which is initiated by leukocyte migration to the inflamed lesion. Hence, genes implicated in the early stages of inflammation are potential therapeutic targets to effectively reduce atherogenesis. Algal-derived polysaccharides are one of the most promising sources for pharmaceutical application, although their mechanism of action is still poorly understood. The present study uses a computational method to anticipate the effect of fucoidan and alginate on interactions with adhesion molecules and chemokine, followed by an assessment of the cytotoxicity of the best-predicted bioactive compound for human monocytic THP-1 macrophages by lactate dehydrogenase and crystal violet assay. Moreover, an in vitro pharmacodynamics evaluation was performed. Molecular docking results indicate that fucoidan has a greater affinity for L-and E-selectin, monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) as compared to alginate. Interestingly, there was no fucoidan cytotoxicity on THP-1 macrophages, even at 200 µg/mL for 24 h. The strong interaction between fucoidan and L-selectin in silico explained its ability to inhibit the THP-1 monocytes migration in vitro. MCP-1 and ICAM-1 expression levels in THP-1 macrophages treated with 50 µg/mL fucoidan for 24 h, followed by induction by IFN-γ, were shown to be significantly suppressed as eight- and four-fold changes, respectively, relative to cells treated only with IFN-γ. These results indicate that the electrostatic interaction of fucoidan improves its binding affinity to inflammatory markers in silico and reduces their expression in THP-1 cells in vitro, thus making fucoidan a good candidate to prevent inflammation. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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13 pages, 1038 KiB

Open AccessArticle

Physicochemical and Microbiological Stability of Two Oral Solutions of Methadone Hydrochloride 10 mg/mL

by Elena Alba Álvaro-Alonso, Ma Paz Lorenzo, Andrea Gonzalez-Prieto, Elsa Izquierdo-García, Ismael Escobar-Rodríguez and Antonio Aguilar-Ros

Molecules 2022, 27(9), 2812; https://doi.org/10.3390/molecules27092812 - 28 Apr 2022

Cited by 4 | Viewed by 2690

Abstract

In this article, we studied physicochemical and microbiological stability and determined the beyond-use date of two oral solutions of methadone in three storage conditions. For this, two oral solutions of methadone (10 mg/mL) were prepared, with and without parabens, as preservatives. They were packed in amber glass vials kept unopened until the day of the test, and in a multi-dose umber glass bottle opened daily. They were stored at 5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C. pH, clarity, and organoleptic characteristics were obtained. A stability-indicating high-performance liquid chromatography method was used to determine methadone. Microbiological quality was studied and antimicrobial effectiveness testing was also determined following European Pharmacopoeia guidelines. Samples were analyzed at days 0, 7, 14, 21, 28, 42, 56, 70, and 91 in triplicate. After 91 days of storage, pH remained stable at about 6.5–7 in the two solutions, ensuring no risk of methadone precipitation. The organoleptic characteristics remained stable (colorless, odorless, and bitter taste). The absence of particles was confirmed. No differences were found with the use of preservatives. Methadone concentration remained within 95–105% in all samples. No microbial growth was observed. Hence, the two oral methadone solutions were physically and microbiologically stable at 5 ± 3 °C, 25 ± 2 °C, and 40 ± 2 °C for 91 days in closed and opened amber glass bottles. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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19 pages, 5074 KiB

Open AccessArticle

Lithium Ascorbate as a Promising Neuroprotector: Fundamental and Experimental Studies of an Organic Lithium Salt

by Ivan Yu. Torshin, Olga A. Gromova, Konstantin S. Ostrenko, Marina V. Filimonova, Irina V. Gogoleva, Vladimir I. Demidov and Alla G. Kalacheva

Molecules 2022, 27(7), 2253; https://doi.org/10.3390/molecules27072253 - 30 Mar 2022

Cited by 11 | Viewed by 3023

Abstract

Given the observable toxicity of lithium carbonate, neuropharmacology requires effective and non-toxic lithium salts. In particular, these salts can be employed as neuroprotective agents since lithium ions demonstrate neuroprotective properties through inhibition of glycogen synthetase kinase-3β and other target proteins, increasing concentrations of endogenous neurotrofic factors. The results of theoretical and experimental studies of organic lithium salts presented here indicate their potential as neuroprotectors. Chemoreactomic modeling of lithium salts made it possible to select lithium ascorbate as a suitable candidate for further research. A neurocytological study on cerebellar granular neurons in culture under conditions of moderate glutamate stress showed that lithium ascorbate was more effective in supporting neuronal survival than chloride or carbonate, i.e., inorganic lithium salts. Biodistribution studies indicated accumulation of lithium ions in a sort of “depot”, potentially consisting of the brain, aorta, and femur. Lithium ascorbate is characterized by extremely low acute and chronic toxicity (LD50 > 5000 mg/kg) and also shows a moderate antitumor effect when used in doses studied (5 or 10 mg/kg). Studies on the model of alcohol intoxication in rats have shown that intake of lithium ascorbate in doses either 5, 10 or 30 mg/kg did not only reduced brain damage due to ischemia, but also improved the preservation of myelin sheaths of neurons. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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19 pages, 4457 KiB

Open AccessArticle

Protective Effect of Quercetin 3-O-Glucuronide against Cisplatin Cytotoxicity in Renal Tubular Cells

by Daniel Muñoz-Reyes, Alfredo G. Casanova, Ana María González-Paramás, Ángel Martín, Celestino Santos-Buelga, Ana I. Morales, Francisco J. López-Hernández and Marta Prieto

Molecules 2022, 27(4), 1319; https://doi.org/10.3390/molecules27041319 - 15 Feb 2022

Cited by 10 | Viewed by 3380

Abstract

Quercetin, a flavonoid with promising therapeutic potential, has been shown to protect from cisplatin nephrotoxicity in rats following intraperitoneal injection, but its low bioavailability curtails its prospective clinical utility in oral therapy. We recently developed a micellar formulation (P-quercetin) with enhanced solubility and bioavailability, and identical nephroprotective properties. As a first aim, we herein evaluated the oral treatment with P-quercetin in rats, which displayed no nephroprotection. In order to unravel this discrepancy, quercetin and its main metabolites were measured by HPLC in the blood and urine after intraperitoneal and oral administrations. Whilst quercetin was absorbed similarly, the profile of its metabolites was different, which led us to hypothesize that nephroprotection might be exerted in vivo by a metabolic derivate. Consequently, we then aimed to evaluate the cytoprotective capacity of quercetin and its main metabolites (quercetin 3-O-glucoside, rutin, tamarixetin, isorhamnetin and quercetin 3-O-glucuronide) against cisplatin toxicity, in HK-2 and NRK-52E tubular cell lines. Cells were incubated for 6 h with quercetin, its metabolites or vehicle (pretreatment), and subsequently 18 h in cotreatment with 10–300 μM cisplatin. Immediately after treatment, cell cultures were subject to the MTT technique as an index of cytotoxicity and photographed under light microscopy for phenotypic assessment. Quercetin afforded no direct cytoprotection and quercetin-3-O-glucuronide was the only metabolite partially preventing the effect of cisplatin in cultured tubule cells. Our results identify a metabolic derivative of quercetin contributing to its nephroprotection and prompt to further explore exogenous quercetin-3-O-glucuronide in the prophylaxis of tubular nephrotoxicity. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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16 pages, 1996 KiB

Open AccessArticle

Carrageenan of Red Algae Eucheuma gelatinae: Extraction, Antioxidant Activity, Rheology Characteristics, and Physicochemistry Characterization

by Hoang Thai Ha, Dang Xuan Cuong, Le Huong Thuy, Pham Thanh Thuan, Dang Thi Thanh Tuyen, Vu Thi Mo and Dinh Huu Dong

Molecules 2022, 27(4), 1268; https://doi.org/10.3390/molecules27041268 - 14 Feb 2022

Cited by 22 | Viewed by 5272

Abstract

Carrageenan is an anionic sulfated polysaccharide that accounts for a high content of red seaweed Eucheuma gelatinae. This paper focused on the extraction, optimization, and evaluation of antioxidant activity, rheology characteristics, and physic-chemistry characterization of β-carrageenan from Eucheuma gelatinae. The extraction and the optimization of β-carrageenan were by the maceration-stirred method and the experimental model of Box-Behken. Antioxidant activity was evaluated to be the total antioxidant activity and reducing power activity. The rheology characteristics of carrageenan were measured to be gel strength and viscosity. Physic-chemistry characterization was determined, including the molecular weight, sugar composition, function groups, and crystal structure, through GCP, GC-FID, FTIR, and XRD. The results showed that carrageenan possessed antioxidant activity, had intrinsic viscosity and gel strength, corresponding to 263.02 cps and 487.5 g/cm², respectively. Antioxidant carrageenan is composed of rhamnose, mannose, glucose, fucose, and xylose, with two molecular weight fractions of 2.635 × 10⁶ and 2.58 × 10⁶ g/mol, respectively. Antioxidant carrageenan did not exist in the crystal. The optimization condition of antioxidant carrageenan extraction was done at 82.35 °C for 115.35 min with a solvent-to-algae ratio of 36.42 (v/w). At the optimization condition, the extraction efficiency of carrageenan was predicted to be 87.56 ± 5.61 (%), the total antioxidant activity and reducing power activity were predicted to 71.95 ± 5.32 (mg ascorbic acid equivalent/g DW) and 89.84 ± 5.84 (mg FeSO₄ equivalent/g DW), respectively. Purity carrageenan content got the highest value at 42.68 ± 2.37 (%, DW). Antioxidant carrageenan from Eucheuma gelatinae is of potential use in food and pharmaceuticals. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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17 pages, 19022 KiB

Open AccessArticle

Molecular Docking and Dynamics Investigations for Identifying Potential Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2: Repurposing of Approved Pyrimidonic Pharmaceuticals for COVID-19 Treatment

by Amin Osman Elzupir

Molecules 2021, 26(24), 7458; https://doi.org/10.3390/molecules26247458 - 9 Dec 2021

Cited by 12 | Viewed by 3079

Abstract

This study demonstrates the inhibitory effect of 42 pyrimidonic pharmaceuticals (PPs) on the 3-chymotrypsin-like protease of SARS-CoV-2 (3CL^pro) through molecular docking, molecular dynamics simulations, and free binding energies by means of molecular mechanics–Poisson Boltzmann surface area (MM-PBSA) and molecular mechanics–generalized Born surface area (MM-GBSA). Of these tested PPs, 11 drugs approved by the US Food and Drug Administration showed an excellent binding affinity to the catalytic residues of 3CL^pro of His41 and Cys145: uracil mustard, cytarabine, floxuridine, trifluridine, stavudine, lamivudine, zalcitabine, telbivudine, tipiracil, citicoline, and uridine triacetate. Their percentage of residues involved in binding at the active sites ranged from 56 to 100, and their binding affinities were in the range from −4.6 ± 0.14 to −7.0 ± 0.19 kcal/mol. The molecular dynamics as determined by a 200 ns simulation run of solvated docked complexes confirmed the stability of PP conformations that bound to the catalytic dyad and the active sites of 3CL^pro. The free energy of binding also demonstrates the stability of the PP–3CL^pro complexes. Citicoline and uridine triacetate showed free binding energies of −25.53 and −7.07 kcal/mol, respectively. Therefore, I recommend that they be repurposed for the fight against COVID-19, following proper experimental and clinical validation. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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12 pages, 3512 KiB

Open AccessArticle

Selective Oxidation of Clopidogrel by Peroxymonosulfate (PMS) and Sodium Halide (NaX) System: An NMR Study

by Everaldo F. Krake and Wolfgang Baumann

Molecules 2021, 26(19), 5921; https://doi.org/10.3390/molecules26195921 - 29 Sep 2021

Cited by 4 | Viewed by 2417

Abstract

A selective transformation of clopidogrel hydrogen sulfate (CLP) by reactive halogen species (HOX) generated from peroxymonosulfate (PMS) and sodium halide (NaX) is described. Other sustainable oxidants as well as different solvents have also been investigated. As result of this study, for each sodium salt the reaction conditions were optimized, and four different degradation products were formed. Three products were halogenated at C-2 on the thiophene ring and have concomitant functional transformation, such as N-oxide in the piperidine group. A halogenated endo-iminium product was also observed. With this condition, a fast preparation of known endo-iminium clopidogrel impurity (new counterion) was reported as well. The progress of the reaction was monitored using nuclear magnetic resonance spectroscopy as an analytical tool and all the products were characterized by 1D-, 2D-NMR and HRMS. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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13 pages, 1941 KiB

Open AccessEditor’s ChoiceArticle

Selenoxide Elimination Triggers Enamine Hydrolysis to Primary and Secondary Amines: A Combined Experimental and Theoretical Investigation

by Giovanni Ribaudo, Marco Bortoli, Erika Oselladore, Alberto Ongaro, Alessandra Gianoncelli, Giuseppe Zagotto and Laura Orian

Molecules 2021, 26(9), 2770; https://doi.org/10.3390/molecules26092770 - 8 May 2021

Cited by 6 | Viewed by 3923

Abstract

We discuss a novel selenium-based reaction mechanism consisting in a selenoxide elimination-triggered enamine hydrolysis. This one-pot model reaction was studied for a set of substrates. Under oxidative conditions, we observed and characterized the formation of primary and secondary amines as elimination products of such compounds, paving the way for a novel strategy to selectively release bioactive molecules. The underlying mechanism was investigated using NMR, mass spectrometry and density functional theory (DFT). Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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13 pages, 2423 KiB

Open AccessArticle

Molecular Docking Study on Several Benzoic Acid Derivatives against SARS-CoV-2

by Amalia Stefaniu, Lucia Pirvu, Bujor Albu and Lucia Pintilie

Molecules 2020, 25(24), 5828; https://doi.org/10.3390/molecules25245828 - 10 Dec 2020

Cited by 19 | Viewed by 6161

Abstract

Several derivatives of benzoic acid and semisynthetic alkyl gallates were investigated by an in silico approach to evaluate their potential antiviral activity against SARS-CoV-2 main protease. Molecular docking studies were used to predict their binding affinity and interactions with amino acids residues from the active binding site of SARS-CoV-2 main protease, compared to boceprevir. Deep structural insights and quantum chemical reactivity analysis according to Koopmans’ theorem, as a result of density functional theory (DFT) computations, are reported. Additionally, drug-likeness assessment in terms of Lipinski’s and Weber’s rules for pharmaceutical candidates, is provided. The outcomes of docking and key molecular descriptors and properties were forward analyzed by the statistical approach of principal component analysis (PCA) to identify the degree of their correlation. The obtained results suggest two promising candidates for future drug development to fight against the coronavirus infection. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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Review

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19 pages, 1440 KiB

Open AccessReview

The Role of Organic Small Molecules in Pain Management

by Sebastián A. Cuesta and Lorena Meneses

Molecules 2021, 26(13), 4029; https://doi.org/10.3390/molecules26134029 - 1 Jul 2021

Cited by 11 | Viewed by 5018

Abstract

In this review, a timeline starting at the willow bark and ending in the latest discoveries of analgesic and anti-inflammatory drugs will be discussed. Furthermore, the chemical features of the different small organic molecules that have been used in pain management will be studied. Then, the mechanism of different types of pain will be assessed, including neuropathic pain, inflammatory pain, and the relationship found between oxidative stress and pain. This will include obtaining insights into the cyclooxygenase action mechanism of nonsteroidal anti-inflammatory drugs (NSAID) such as ibuprofen and etoricoxib and the structural difference between the two cyclooxygenase isoforms leading to a selective inhibition, the action mechanism of pregabalin and its use in chronic neuropathic pain, new theories and studies on the analgesic action mechanism of paracetamol and how changes in its structure can lead to better characteristics of this drug, and cannabinoid action mechanism in managing pain through a cannabinoid receptor mechanism. Finally, an overview of the different approaches science is taking to develop more efficient molecules for pain treatment will be presented. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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Other

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13 pages, 2323 KiB

Open AccessPerspective

Drug Design: Where We Are and Future Prospects

by Giuseppe Zagotto and Marco Bortoli

Molecules 2021, 26(22), 7061; https://doi.org/10.3390/molecules26227061 - 22 Nov 2021

Cited by 8 | Viewed by 4144

Abstract

Medicinal chemistry is facing new challenges in approaching precision medicine. Several powerful new tools or improvements of already used tools are now available to medicinal chemists to help in the process of drug discovery, from a hit molecule to a clinically used drug. Among the new tools, the possibility of considering folding intermediates or the catalytic process of a protein as a target for discovering new hits has emerged. In addition, machine learning is a new valuable approach helping medicinal chemists to discover new hits. Other abilities, ranging from the better understanding of the time evolution of biochemical processes to the comprehension of the biological meaning of the data originated from genetic analyses, are on their way to progress further in the drug discovery field toward improved patient care. In this sense, the new approaches to the delivery of drugs targeted to the central nervous system, together with the advancements in understanding the metabolic pathways for a growing number of drugs and relating them to the genetic characteristics of patients, constitute important progress in the field. Full article

(This article belongs to the Special Issue From a Molecule to a Drug: Chemical Features Enhancing Pharmacological Potential)

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