Pharmaceuticals

Research

Jump to: Review

20 pages, 2841 KiB

Open AccessArticle

New InhA Inhibitors Based on Expanded Triclosan and Di-Triclosan Analogues to Develop a New Treatment for Tuberculosis

by Sarentha Chetty, Tom Armstrong, Shalu Sharma Kharkwal, William C. Drewe, Cristina I. De Matteis, Dimitrios Evangelopoulos, Sanjib Bhakta and Neil R. Thomas

Pharmaceuticals 2021, 14(4), 361; https://doi.org/10.3390/ph14040361 - 14 Apr 2021

Cited by 15 | Viewed by 4308

Abstract

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has reinforced the need for the development of new anti-TB drugs. The first line drug isoniazid inhibits InhA. This is a prodrug requiring activation by the enzyme KatG. Mutations in KatG have [...] Read more.

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has reinforced the need for the development of new anti-TB drugs. The first line drug isoniazid inhibits InhA. This is a prodrug requiring activation by the enzyme KatG. Mutations in KatG have largely contributed to clinical isoniazid resistance. We aimed to design new ‘direct’ InhA inhibitors that obviate the need for activation by KatG, circumventing pre-existing resistance. In silico molecular modelling was used as part of a rational structure-based drug-design approach involving inspection of protein crystal structures of InhA:inhibitor complexes, including the broad spectrum antibiotic triclosan (TCS). One crystal structure exhibited the unusual presence of two triclosan molecules within the Mycobacterium tuberculosis InhA binding site. This became the basis of a strategy for the synthesis of novel inhibitors. A series of new, flexible ligands were designed and synthesised, expanding on the triclosan structure. Low Minimum Inhibitory Concentrations (MICs) were obtained for benzylphenyl compounds (12, 43 and 44) and di-triclosan derivative (39), against Mycobacterium bovis BCG although these may also be inhibiting other enzymes. The ether linked di-triclosan derivative (38) displayed excellent in vitro isolated enzyme inhibition results comparable with triclosan, but at a higher MIC (125 µg mL⁻¹). These compounds offer good opportunities as leads for further optimisation. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Graphical abstract

17 pages, 1805 KiB

Open AccessArticle

Monosubstituted Acetophenone Thiosemicarbazones as Potent Inhibitors of Tyrosinase: Synthesis, Inhibitory Studies, and Molecular Docking

by Katarzyna Hałdys, Waldemar Goldeman, Natalia Anger-Góra, Joanna Rossowska and Rafał Latajka

Pharmaceuticals 2021, 14(1), 74; https://doi.org/10.3390/ph14010074 - 18 Jan 2021

Cited by 23 | Viewed by 3919

Abstract

A set of 12 monosubstituted acetophenone thiosemicarbazone derivatives (TSCs) were synthesized and their inhibitory properties toward tyrosinase activity were tested. Moreover, their ability to inhibit melanogenesis in the B16F10 murine melanoma cell line was studied. In order to investigate the nature of interactions [...] Read more.

A set of 12 monosubstituted acetophenone thiosemicarbazone derivatives (TSCs) were synthesized and their inhibitory properties toward tyrosinase activity were tested. Moreover, their ability to inhibit melanogenesis in the B16F10 murine melanoma cell line was studied. In order to investigate the nature of interactions between the enzyme and the inhibitors, molecular docking to the active site was performed. TSCs 5, 6, 8, and 9 revealed a half maximal inhibitory concentration (IC₅₀) below 1 µM. Compound 6 turned out to be the most potent tyrosinase inhibitor. All investigated compounds showed reversible inhibition of competitive or mixed type. The para-substituted TSCs had higher affinity for the enzyme as compared to their ortho- and meta-analogues. All investigated compounds inhibited melanin production in B16F10 cells at the micromolar level. Molecular docking showed that the sulfur atom of the thiourea moiety penetrates the active site and interacts with copper ions. The above outcomes might be helpful in the design of new tyrosinase inhibitors in the food and cosmetic industries. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Figure 1

17 pages, 3316 KiB

Open AccessArticle

Repurposing the McoTI-II Rigid Molecular Scaffold in to Inhibitor of ‘Papain Superfamily’ Cysteine Proteases

by Manasi Mishra, Vigyasa Singh, Meenakshi B. Tellis, Rakesh S. Joshi and Shailja Singh

Pharmaceuticals 2021, 14(1), 7; https://doi.org/10.3390/ph14010007 - 23 Dec 2020

Cited by 5 | Viewed by 2816

Abstract

Clan C1A or ‘papain superfamily’ cysteine proteases are key players in many important physiological processes and diseases in most living systems. Novel approaches towards the development of their inhibitors can open new avenues in translational medicine. Here, we report a novel design of [...] Read more.

Clan C1A or ‘papain superfamily’ cysteine proteases are key players in many important physiological processes and diseases in most living systems. Novel approaches towards the development of their inhibitors can open new avenues in translational medicine. Here, we report a novel design of a re-engineered chimera inhibitor Mco-cysteine protease inhibitor (CPI) to inhibit the activity of C1A cysteine proteases. This was accomplished by grafting the cystatin first hairpin loop conserved motif (QVVAG) onto loop 1 of the ultrastable cyclic peptide scaffold McoTI-II. The recombinantly expressed Mco-CPI protein was able to bind with micromolar affinity to papain and showed remarkable thermostability owing to the formation of multi-disulphide bonds. Using an in silico approach based on homology modelling, protein–protein docking, the calculation of the free-energy of binding, the mechanism of inhibition of Mco-CPI against representative C1A cysteine proteases (papain and cathepsin L) was validated. Furthermore, molecular dynamics simulation of the Mco-CPI–papain complex validated the interaction as stable. To conclude, in this McoTI-II analogue, the specificity had been successfully redirected towards C1A cysteine proteases while retaining the moderate affinity. The outcomes of this study pave the way for further modifications of the Mco-CPI design for realizing its full potential in therapeutics. This study also demonstrates the relevance of ultrastable peptide-based scaffolds for the development of novel inhibitors via grafting. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Graphical abstract

24 pages, 3725 KiB

Open AccessArticle

Novel Isoniazid-Carborane Hybrids Active In Vitro against Mycobacterium tuberculosis

by Daria Różycka, Małgorzata Korycka-Machała, Anna Żaczek, Jarosław Dziadek, Dorota Gurda, Marta Orlicka-Płocka, Eliza Wyszko, Katarzyna Biniek-Antosiak, Wojciech Rypniewski and Agnieszka B. Olejniczak

Pharmaceuticals 2020, 13(12), 465; https://doi.org/10.3390/ph13120465 - 15 Dec 2020

Cited by 11 | Viewed by 2898

Abstract

Tuberculosis (TB) is a severe infectious disease with high mortality and morbidity. The emergence of drug-resistant TB has increased the challenge to eliminate this disease. Isoniazid (INH) remains the key and effective component in the therapeutic regimen recommended by World Health Organization (WHO). [...] Read more.

Tuberculosis (TB) is a severe infectious disease with high mortality and morbidity. The emergence of drug-resistant TB has increased the challenge to eliminate this disease. Isoniazid (INH) remains the key and effective component in the therapeutic regimen recommended by World Health Organization (WHO). A series of isoniazid-carborane derivatives containing 1,2-dicarba-closo-dodecaborane, 1,7-dicarba-closo-dodecaborane, 1,12-dicarba-closo-dodecaborane, or 7,8-dicarba-nido-undecaborate anion were synthesized for the first time. The compounds were tested in vitro against the Mycobacterium tuberculosis (Mtb) H37Rv strain and its mutant (ΔkatG) defective in the synthesis of catalase-peroxidase (KatG). N′-((7,8-dicarba-nido-undecaboranyl)methylidene)isonicotinohydrazide (16) showed the highest activity against the wild-type Mtb strain. All hybrids could inhibit the growth of the ΔkatG mutant in lower concentrations than INH. N′-([(1,12-dicarba-closo-dodecaboran-1yl)ethyl)isonicotinohydrazide (25) exhibited more than 60-fold increase in activity against Mtb ΔkatG as compared to INH. This compound was also found to be noncytotoxic up to a concentration four times higher than the minimum inhibitory concentration 99% (MIC₉₉) value. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Graphical abstract

23 pages, 6936 KiB

Open AccessArticle

Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

by Tarek S. Ibrahim, Mohamed M. Hawwas, Azizah M. Malebari, Ehab S. Taher, Abdelsattar M. Omar, Niamh M. O'Boyle, Eavan McLoughlin, Zakaria K. Abdel-Samii and Yaseen A. M. M. Elshaier

Pharmaceuticals 2020, 13(11), 393; https://doi.org/10.3390/ph13110393 - 15 Nov 2020

Cited by 14 | Viewed by 3326

Abstract

A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most [...] Read more.

A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound, 19h, demonstrated superior IC₅₀ values ranging from 0.02 to 0.04 µM against four cancer cell lines while maintaining low cytotoxicity in MCF-10A non-cancer cells, thereby suggesting 19h’s selectivity towards proliferating cancer cells. In addition to tubulin polymerization inhibition, 19h caused cell cycle arrest in MCF-7 cells at the G2/M phase and induced apoptosis. Collectively, these findings indicate that 19h holds potential for further investigation as a potent chemotherapeutic agent targeting tubulin. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Graphical abstract

25 pages, 3323 KiB

Open AccessArticle

Synthesis, 3D-QSAR, and Molecular Modeling Studies of Triazole Bearing Compounds as a Promising Scaffold for Cyclooxygenase-2 Inhibition

by Ranza Elrayess, Mohamed Saleh Elgawish, Marwa Elewa, Mohamed S. Nafie, Sameh S. Elhady and Asmaa S. A. Yassen

Pharmaceuticals 2020, 13(11), 370; https://doi.org/10.3390/ph13110370 - 06 Nov 2020

Cited by 5 | Viewed by 3097

Abstract

Targeting of cyclooxygenase-2 (COX-2) has emerged as a powerful tool for therapeutic intervention because the overexpression of this enzyme is synonymous with inflammation, cancer, and neurodegenerative diseases. Herein, a new series of 1,2,4-triazole Schiff bases scaffold with aryl and heteroaryl systems 9a–12d were [...] Read more.

Targeting of cyclooxygenase-2 (COX-2) has emerged as a powerful tool for therapeutic intervention because the overexpression of this enzyme is synonymous with inflammation, cancer, and neurodegenerative diseases. Herein, a new series of 1,2,4-triazole Schiff bases scaffold with aryl and heteroaryl systems 9a–12d were designed, synthesized, structurally elucidated, and biologically evaluated as a potent COX-2 blocker. The rationale beyond the current study is to increase the molecule bulkiness allowing a selective binding to the unique hydrophobic pocket of COX-2. Among the triazole–thiazole hybrids, the one with the para-methoxy moiety linked to a phenyl ring 12d showed the highest In vitro selectivity by COX-2 inhibition assay (IC₅₀ of 0.04 μM) and in situ anti-inflammatory activity when evaluated using the protein denaturation assay (IC₅₀ of 0.88 μM) in comparison with commercially available selective COX-2 inhibitor, Celecoxib (IC₅₀ of 0.05 μM). Towards the COX-2 selectivity, ligand-based three dimensional quantitative structures activity relationship (3D-QSAR) employing atomic-based and field-based approaches were performed and resulted in the necessity of triazole and thiazole/oxazole scaffolds for COX-2 blocking. Furthermore, the molecular modeling study indicated a high selectivity and promising affinity of our prepared compounds to COX-2, especially the hydrophobic pocket and the mouth of the active site holding hydrogen-bonding, hydrophobic, and electrostatic interactions. In Silico absorption, delivery, metabolism, and excretion (ADME) predictions showed that all the pharmacokinetic and physicochemical features are within the appropriate range for human use. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Graphical abstract

42 pages, 11454 KiB

Open AccessArticle

A Proline-Based Tectons and Supramolecular Synthons for Drug Design 2.0: A Case Study of ACEI

by Joanna Bojarska, Milan Remko, Martin Breza, Izabela Madura, Andrzej Fruziński and Wojciech M. Wolf

Pharmaceuticals 2020, 13(11), 338; https://doi.org/10.3390/ph13110338 - 24 Oct 2020

Cited by 10 | Viewed by 4389

Abstract

Proline is a unique, endogenous amino acid, prevalent in proteins and essential for living organisms. It is appreciated as a tecton for the rational design of new bio-active substances. Herein, we present a short overview of the subject. We analyzed 2366 proline-derived structures [...] Read more.

Proline is a unique, endogenous amino acid, prevalent in proteins and essential for living organisms. It is appreciated as a tecton for the rational design of new bio-active substances. Herein, we present a short overview of the subject. We analyzed 2366 proline-derived structures deposited in the Cambridge Structure Database, with emphasis on the angiotensin-converting enzyme inhibitors. The latter are the first-line antihypertensive and cardiological drugs. Their side effects prompt a search for improved pharmaceuticals. Characterization of tectons (molecular building blocks) and the resulting supramolecular synthons (patterns of intermolecular interactions) involving proline derivatives, as presented in this study, may be useful for in silico molecular docking and macromolecular modeling studies. The DFT, Hirshfeld surface and energy framework methods gave considerable insight into the nature of close inter-contacts and supramolecular topology. Substituents of proline entity are important for the formation and cooperation of synthons. Tectonic subunits contain proline moieties characterized by diverse ionization states: -N and -COOH(-COO⁻), -N⁺ and -COOH(-COO⁻), -NH and -COOH(-COO⁻), -NH⁺ and -COOH(-COO⁻), and -NH₂⁺ and -COOH(-COO⁻). Furthermore, pharmacological profiles of ACE inhibitors and their impurities were determined via an in silico approach. The above data were used to develop comprehensive classification, which may be useful in further drug design studies. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Graphical abstract

26 pages, 4088 KiB

Open AccessArticle

Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach

by Rozires P. Leão, Josiane V. Cruz, Glauber V. da Costa, Jorddy N. Cruz, Elenilze F. B. Ferreira, Raí C. Silva, Lúcio R. de Lima, Rosivaldo S. Borges, Gabriela B. dos Santos and Cleydson B. R. Santos

Pharmaceuticals 2020, 13(9), 209; https://doi.org/10.3390/ph13090209 - 26 Aug 2020

Cited by 49 | Viewed by 5517

Abstract

The cyclooxygenase-2 receptor is a therapeutic target for planning potential drugs with anti-inflammatory activity. The selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was selected as a pivot molecule to perform virtual ligand-based screening from six commercial databases. We performed the search for similarly shaped Rapid [...] Read more.

The cyclooxygenase-2 receptor is a therapeutic target for planning potential drugs with anti-inflammatory activity. The selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was selected as a pivot molecule to perform virtual ligand-based screening from six commercial databases. We performed the search for similarly shaped Rapid Overlay of Chemical Structures (ROCS) and electrostatic (EON) compounds. After, we used pharmacokinetic and toxicological parameters to determine the best potential compounds, obtained through the softwares QikProp and Derek, respectively. Then, the compounds proceeded to the molecular anchorage study, which showed promising results of binding affinity with the hCOX-2 receptor: LMQC72 (∆G = −11.0 kcal/mol), LMQC36 (∆G = −10.6 kcal/mol), and LMQC50 (∆G = −10.2 kcal/mol). LMQC72 and LMQC36 showed higher binding affinity compared to rofecoxib (∆G = −10.4 kcal/mol). Finally, molecular dynamics (MD) simulations were used to evaluate the interaction of the compounds with the target hCOX-2 during 150 ns. In all MD simulation trajectories, the ligands remained interacting with the protein until the end of the simulation. The compounds were also complexing with hCOX-2 favorably. The compounds obtained the following affinity energy values: rofecoxib: ΔGbind = −45.31 kcal/mol; LMQC72: ΔGbind = −38.58 kcal/mol; LMQC36: ΔGbind = −36.10 kcal/mol; and LMQC50: ΔGbind = −39.40 kcal/mol. The selected LMQC72, LMQC50, and LMQC36 structures showed satisfactory pharmacokinetic results related to absorption and distribution. The toxicological predictions of these compounds did not display alerts for possible toxic groups and lower risk of cardiotoxicity compared to rofecoxib. Therefore, future in vitro and in vivo studies are needed to confirm the anti-inflammatory potential of the compounds selected here with bioinformatics approaches based on rofecoxib ligand. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Graphical abstract

22 pages, 12198 KiB

Open AccessArticle

Design and Development of Novel Urea, Sulfonyltriurea, and Sulfonamide Derivatives as Potential Inhibitors of Sphingosine Kinase 1

by Sonam Roy, Amarjyoti Das Mahapatra, Taj Mohammad, Preeti Gupta, Mohamed F. Alajmi, Afzal Hussain, Md. Tabish Rehman, Bhaskar Datta and Md. Imtaiyaz Hassan

Pharmaceuticals 2020, 13(6), 118; https://doi.org/10.3390/ph13060118 - 09 Jun 2020

Cited by 12 | Viewed by 4226

Abstract

Sphingosine kinase 1 (SphK1) is one of the well-studied drug targets for cancer and inflammatory diseases. Recently discovered small-molecule inhibitors of SphK1 have been recommended in cancer therapeutics; however, selectivity and potency of first-generation inhibitors are great challenge. In search of effective SphK1 [...] Read more.

Sphingosine kinase 1 (SphK1) is one of the well-studied drug targets for cancer and inflammatory diseases. Recently discovered small-molecule inhibitors of SphK1 have been recommended in cancer therapeutics; however, selectivity and potency of first-generation inhibitors are great challenge. In search of effective SphK1 inhibitors, a set of small molecules have been designed and synthesized bearing urea, sulfonylurea, sulfonamide, and sulfonyltriurea groups. The binding affinity of these inhibitors was measured by fluorescence-binding assay and isothermal titration calorimetry. Compounds 1, 5, 6, and 7 showed an admirable binding affinity to the SphK1 in the sub-micromolar range and significantly inhibited SphK1 activity with admirable IC₅₀ values. Molecular docking studies revealed that these compounds fit well into the sphingosine binding pocket of SphK1 and formed significant number of hydrogen bonds and van der Waals interactions. These molecules may be exploited as potent and selective inhibitors of SphK1 that could be implicated in cancer therapeutics after the required in vivo validation. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Graphical abstract

Review

Jump to: Research

40 pages, 885 KiB

Open AccessReview

Bowman-Birk Inhibitors: Insights into Family of Multifunctional Proteins and Peptides with Potential Therapeutical Applications

by Agata Gitlin-Domagalska, Aleksandra Maciejewska and Dawid Dębowski

Pharmaceuticals 2020, 13(12), 421; https://doi.org/10.3390/ph13120421 - 25 Nov 2020

Cited by 37 | Viewed by 4518

Abstract

Bowman-Birk inhibitors (BBIs) are found primarily in seeds of legumes and in cereal grains. These canonical inhibitors share a highly conserved nine-amino acids binding loop motif CTP1SXPPXC (where P1 is the inhibitory active site, while X stands for various amino acids). They are [...] Read more.

Bowman-Birk inhibitors (BBIs) are found primarily in seeds of legumes and in cereal grains. These canonical inhibitors share a highly conserved nine-amino acids binding loop motif CTP1SXPPXC (where P1 is the inhibitory active site, while X stands for various amino acids). They are natural controllers of plants’ endogenous proteases, but they are also inhibitors of exogenous proteases present in microbials and insects. They are considered as plants’ protective agents, as their elevated levels are observed during injury, presence of pathogens, or abiotic stress, i.a. Similar properties are observed for peptides isolated from amphibians’ skin containing 11-amino acids disulfide-bridged loop CWTP1SXPPXPC. They are classified as Bowman-Birk like trypsin inhibitors (BBLTIs). These inhibitors are resistant to proteolysis and not toxic, and they are reported to be beneficial in the treatment of various pathological states. In this review, we summarize up-to-date research results regarding BBIs’ and BBLTIs’ inhibitory activity, immunomodulatory and anti-inflammatory activity, antimicrobial and insecticidal strength, as well as chemopreventive properties. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Graphical abstract

17 pages, 3104 KiB

Open AccessReview

Papain-Like Proteases as Coronaviral Drug Targets: Current Inhibitors, Opportunities, and Limitations

by Anastasiia I. Petushkova and Andrey A. Zamyatnin, Jr.

Pharmaceuticals 2020, 13(10), 277; https://doi.org/10.3390/ph13100277 - 28 Sep 2020

Cited by 33 | Viewed by 4785

Abstract

Papain-like proteases (PLpro) of coronaviruses (CoVs) support viral reproduction and suppress the immune response of the host, which makes CoV PLpro perspective pharmaceutical targets. Their inhibition could both prevent viral replication and boost the immune system of the host, leading to the speedy [...] Read more.

Papain-like proteases (PLpro) of coronaviruses (CoVs) support viral reproduction and suppress the immune response of the host, which makes CoV PLpro perspective pharmaceutical targets. Their inhibition could both prevent viral replication and boost the immune system of the host, leading to the speedy recovery of the patient. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third CoV outbreak in the last 20 years. Frequent mutations of the viral genome likely lead to the emergence of more CoVs. Inhibitors for CoV PLpro can be broad-spectrum and can diminish present and prevent future CoV outbreaks as PLpro from different CoVs have conservative structures. Several inhibitors have been developed to withstand SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). This review summarizes the structural features of CoV PLpro, the inhibitors that have been identified over the last 20 years, and the compounds that have the potential to become novel effective therapeutics against CoVs in the near future. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Figure 1

45 pages, 2197 KiB

Open AccessReview

Novel 1,2,4-Oxadiazole Derivatives in Drug Discovery

by Karol Biernacki, Mateusz Daśko, Olga Ciupak, Konrad Kubiński, Janusz Rachon and Sebastian Demkowicz

Pharmaceuticals 2020, 13(6), 111; https://doi.org/10.3390/ph13060111 - 29 May 2020

Cited by 95 | Viewed by 8912

Abstract

Five-membered 1,2,4-oxadiazole heterocyclic ring has received considerable attention because of its unique bioisosteric properties and an unusually wide spectrum of biological activities. Thus, it is a perfect framework for the novel drug development. After a century since the 1,2,4-oxadiazole have been discovered, the [...] Read more.

Five-membered 1,2,4-oxadiazole heterocyclic ring has received considerable attention because of its unique bioisosteric properties and an unusually wide spectrum of biological activities. Thus, it is a perfect framework for the novel drug development. After a century since the 1,2,4-oxadiazole have been discovered, the uncommon potential attracted medicinal chemists’ attention, leading to the discovery of a few presently accessible drugs containing 1,2,4-oxadiazole unit. It is worth noting that the interest in a 1,2,4-oxadiazoles’ biological application has been doubled in the last fifteen years. Herein, after a concise historical introduction, we present a comprehensive overview of the recent achievements in the synthesis of 1,2,4-oxadiazole-based compounds and the major advances in their biological applications in the period of the last five years as well as brief remarks on prospects for further development. Full article

(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs 2020)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Design of Enzyme Inhibitors as Potential Drugs 2020

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issue

Published Papers (12 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI