Medicinal Chemistry - Science topic

Dear Colleagues, After the great success of the first two editions, we are pleased to inform you that Molecules will launch the third edition of the Special Issue “Computational Approaches: Drug Discovery and Design in Medicinal Chemistry and Bioinformatics”. https://www.mdpi.com/journal/molecules/special_issues/ comput_appr_drug_dis_des_med_chem_b...

Sulfamides are significant compounds because of their biological effects on bacteria, fungi, and cancer. The antimicrobial and anticancer properties of sulfamide derivatives have been demonstrated in several microbial strains and cancer cell lines. They have worked mostly in the field of medicinal chemistry. Numerous microbiological pathogens are k...

Article history: Background: Coumarin-based derivatives (Cou-Ds) are one of the most important types of heterocycles, with a wide range of uses in synthetic and medicinal chemistry. Cou-Ds have interested researchers due to their wide range of biomedical potential and application as valuable synthetic scaffolds, which have been instrumental in the...

Two decades after K [...]

This book provides a meticulous view on methodological drug discovery and development insights from bench to bedside. The current book threads almost each step encompassing drug the discovery and development of a molecule. The chapters focus on computational modus operandi, pharmacological optimization approaches, modern high-throughput screening m...

Benzothiazole (1, 3-benzothiazole), a weak base is a crucial pharmacophore in heterocyclic compounds that displays a variety of biological properties due to its potent and significant pharmacological activities. The unique methylene centre at the C2 position present in the thiazole ring makes benzothiazole the most common and integral structure of...

Among the large variety of organic compounds, heterocycles are interesting compounds widely occurring in nature, showing biological activities. Dihydropyridine (DHP) is a privileged scaffold having nitrogen in a six-membered cyclic ring as a central moiety. DHP is a significant compound studied in medicinal chemistry and pharmacology activities. Th...

It is important to precisely predict the intestinal absorption ratio (Fa) at an early stage in the discovery of orally available drugs because it directly influences drug efficacy. Gastrointestinal unified theoretical framework (GUTFW) and machine learning (ML) are commonly used to predict the percentage of Fa. In GUTFW, the Fa of a drug is estimat...

Disease prediction and treatment is an important process, and medicinal chemistry has played an essential role. In this regard, computational approaches help to identify new drugs in a shorter period. The utilization of such cutting-edge research methodologies enables accelerated target identification, protein structure prediction, drug design, and...

While the impact of medicinal chemistry on the design and optimisation of small molecule orally bioavailable drugs is clearly recognised, historically medicinal chemistry has been somewhat overlooked in the field of antibody-drug conjugates (ADCs). This talk will show how the application of established small molecule design techniques can be used t...

Leishmaniasis is caused by protozoans of the genus Leishmania, and its treatment is highly toxic, leading to treatment discontinuation and the emergence of resistant strains. In this study, we assessed the leishmanicidal activity and chemical composition of red propolis collected from the Amazon-dominated region of northern Tocantins State, Brazil....

Protein–fragment complex structures are particularly sought after in medicinal chemistry to rationally design lead molecules. These structures are usually derived using X-ray crystallography, but the failure rate is non-neglectable. NMR is a possible alternative for the calculation of weakly interacting complexes. Nevertheless, the time-consuming p...

New approaches for combatting microbial infections are needed. One strategy for disrupting pathogenesis involves developing compounds that interfere with bacterial virulence. A critical molecular determinant of virulence for Gram-negative bacteria are efflux pumps of the resistance-nodulation-division (RND) family, which includes AcrAB-TolC. We pre...

Small-molecule drugs have enabled the practice of precision oncology for genetically defined patient populations since the first approval of imatinib in 2001. Scientific and technology advances over this 20-year period have driven the evolution of cancer biology, medicinal chemistry, and data science. Collectively, these advances provide tools to m...

The richness of Brazilian biodiversity translates into a valuable collection of molecules with biological properties that range from ecological functions to pharmacological properties. For over 25 years, the Nucleus of Bioassays, Biosynthesis, and Ecophysiology of Natural Products (NuBBE) has conducted extensive investigations into the chemical ent...

Tetrahydropyrazolo[1,5-a]pyrimidine (THPP) is an attractive scaffold for designing biologically active compounds. The most obvious way to obtain such compounds is to reduce pyrazolopyrimidines with complex hydrides, because the pyrimidine ring is reduced in the preference over the pyrazole ring. The presence of substituents at positions five and se...

The assessment of cardiotoxicity is a persistent problem in medicinal chemistry. Quantitative structure–activity relationships (QSAR) are one possible way to build up models for cardiotoxicity. Here, we describe the results obtained with the Monte Carlo technique to develop hybrid optimal descriptors correlated with cardiotoxicity. The predictive p...

The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel whose loss of function leads to cystic fibrosis, while its hyperactivation leads to secretory diarrhea. Small molecules that improve CFTR folding (correctors) or function (potentiators) are clinically available. However, the only potentiator, ivacaftor, has subo...

The utility of quinazoline scaffolds as intermediates in new medicinal drug development and discovery has grown in recent decades. The quinazoline framework is a valuable pharmacophore, intermediate, and interesting building block with a wide range of pharmacological activities that has piqued the interest of researchers in developing novel synthet...

Considering the importance of metal complexes in the development of medicinal chemistry, a series of transition metal complexes of Co(II), Fe(II), Zn(II), Cu(II), and Ni(II) has been synthesized from N,N'-bis(salicylidene)-2,2-dimethyl-1,3-diaminopropane H2L Schiff base ligand. The reaction of the H2L with the selected metal ions led to tetrahedral...

The clinical utility of rifamycins against non-tuberculous mycobacterial (NTM) disease is limited by intrinsic drug resistance achieved by ADP-ribosyltransferase Arr. By blocking the site of ribosylation, we recently optimized a series of analogs with substantially improved potency against Mycobacterium abscessus . Here, we show that a representati...

Alzheimer's disease is a most prevalent form of dementia all around the globe and currently poses a significant challenge to the healthcare system. Currently available drugs only slow the progression of this disease rather than provide proper containment. Identification of multiple targets responsible for this disease in the last three decades esta...

Pan Assay INterference compoundS (PAINS) are known to be a source of false positives in High Throughput Screening (HTS) campaigns. This has become a major problem in medicinal chemistry, often resulting in undesirable project outcomes and increased overall cost. Our recent campaign to identify inhibitors of USP8 that could be used in the treatment...

An important objective in organic synthesis and medicinal chemistry is the capacity to access structurally varied and complex molecules rapidly and affordably from easily available starting materials. Herein, a protocol for the structurally divergent synthesis of benzofuran fused azocine derivatives and spiro-cyclopentanone benzofurans has been dev...

Artificial intelligence (AI) has permeated various sectors, including the pharmaceutical industry and research, where it has been utilized to efficiently identify new chemical entities with desirable properties. The application of AI algorithms to drug discovery presents both remarkable opportunities and challenges. This review article focuses on t...

Natural compounds are rich in pharmacological properties that are a hot topic in pharmaceutical research. The quinoline ring plays important roles in many biological processes in heterocycles. Many pharmacological compounds, including saquinavir and chloroquine, have been marketed as quinoline molecules with good anti-viral and anti-parasitic prope...

Isoxazole belongs to the class of five-membered heterocyclic compounds. The process of developing new drugs has significantly gained attention due to inadequate pharmacokinetic and safety attributes of the available drugs. This study aimed to design a new diverse array of ten novel isoxazole derivatives via Claisen Schmidt condensation reaction. In...

One of the main challenges of medicinal chemistry is the search for new substances with antimicrobial potential that could be used in the fight against pathogenic microorganisms. Therefore, the antimicrobial activity of newly synthesized compounds is still being investigated. Carbazole-containing compounds appear to be promising antibacterial, anti...

The importance of the benzo[b]furan motif becomes evident in the remarkable results of numerous biological investigations, establishing its potential as a robust therapeutic option. This review presents an overview of the synthesis of and exhaustive biological studies conducted on benzo[b]furan derivatives from 2011 to 2022, accentuating their exce...

An electrochemical reaction between quinoline N-oxides and morpholine was developed by using Cu(OAc)2 as a catalyst, generating products of 4-aminoquinoline N-oxides in CH2Cl2 or 2-aminoquinoline N-oxides in CH3CN in good yields. With an increase in the amount of electricity passed, the product deoxygenates with the formation of aminoquinolines. Th...

In immunoglobulin light chain amyloidosis, unstable immunoglobulin light chains aggregate as amyloid fibrils in organs, leading to organ failure and death in more than 50% of untreated patients. Research by Morgan et al. (Morgan, G. J. et. al., Proceedings of the National Academy of Sciences 2019, 116, 8360–8369) and Yan et al. (Yan, N. L. et. al.,...

A series of compounds containing heterocyclic cores and gem-difluorocycloalkyl substituents was obtained under conditions of the parallel synthesis (i.e., simultaneous performance of reaction procedures, treatment of the reaction mixture, and product isolation for a number of similar transformations) using the reductive amination – the “Nitrogen de...

PROTACs represent an emerging field in medicinal chemistry, which has already led to the developmentof compounds that reached clinical studies. Posttranslational modifications contribute to the complexity of proteomes, with 2846 disease-associated sites. PROTAC field is very advanced in targeting kinases, while its use for enzymes mediating posttra...

Proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules that co opt the cell’s natural proteasomal degradation mechanisms to selectively tag and degrade undesired proteins. However, a challenge associated with PROTACs is the difficult optimisation required to identify new degraders, thus the development of high-throughput platform...

Further correction for ‘Expanding medicinal chemistry into 3D space: metallofragments as 3D scaffolds for fragment-based drug discovery’ by Christine N. Morrison et al., Chem. Sci., 2020, 11, 1216–1225, https://doi.org/10.1039/C9SC05586J.

Background: Thiazole ring is one of the most important heterocycle scaffolds in organic and medicinal chemistry due to this scaffold being the backbone of numerous drugs and their significant activities against various diseases have made it one of the best candidates for industrial production. According to the literature, the number of drugs that h...

Histone deacetylases (HDACs) are a class of zinc (Zn)-dependent metalloenzymes that are responsible for epigenetic modifications. HDACs are largely associated with histone proteins that regulate gene expression at the DNA level. This tight regulation is controlled by acetylation [via histone acetyl transferases (HATs)] and deacetylation (via HDACs)...

Bispidines are a family of ligands that plays a pivotal role in various areas of coordination chemistry, with applications in medicinal chemistry, molecular catalysis, coordination polymers synthesis, and molecular magnetism. In the present work, triazole moieties were introduced using the CuAAC click-reaction, with the aim of expanding the number...

In medicinal chemistry, the link between structure and activity is essential. We are seeking to relate chemical structure and reactivity to medicinal properties, which has gained popularity recently. In this study, scaffolds from three antioxidants were changed to new derivatives to show that their biological effects as antioxidants would change. W...

There are over 500 human kinases ranging from very well-studied to almost completely ignored. Kinases are tractable and implicated in many diseases, making them ideal targets for medicinal chemistry campaigns, but is it possible to discover a drug for each individual kinase? For every human kinase, we gathered data on their citation count, availabi...

In this study, several quantum mechanical-based computational approaches have been used in order to propose accurate protocols for predicting the p K a ’s of quinazoline derivatives, which constitute a very important class of natural and synthetic compounds in organic, pharmaceutical, agricultural and medicinal chemistry areas. Linear relationships...

Tupistra clarkei, commonly known as nakima in the local language, belongs to the family Asparagaceae. It is a perennial crop found in the wild as well as growing in the home garden. It prefers shady and moist areas. The edible part of this vegetable is inflorescence which is cooked as a vegetable. It is very rich in nutrients and minerals as well a...

New disease targets and medicinal chemistry approaches are urgently needed to develop novel therapeutic strategies for treating pulmonary diseases. Emerging evidence suggests that reduced activity of protein phosphatase 2A (PP2A), a complex heterotrimeric enzyme that regulates dephosphorylation of serine and threonine residues from many proteins, i...

Multicomponent reactions (MCRs) have emerged as transformative cornerstones in modern drug development, revolutionizing the synthesis of complex molecular architectures. Beyond traditional methods, MCRs offer unparalleled advantages by enabling the concurrent assembly of multiple reactants into intricate structures through a single, streamlined pro...

Sulfonyl and sulfonimidoyl fluorides are versatile substrates in organic synthesis and medicinal chemistry. However, they have been exclusively used as S(VI) ⁺ electrophiles for defluorinative ligations. Converting sulfonyl and sulfonimidoyl fluorides to S(VI) radicals is challenging and underexplored due to the strong bond dissociation energy of S...

In current research, two functional components, i.e., hydrazone and bisphenol sulfide were combined to get useful supramolecules in medicinal chemistry. Herein 25 new 4,4′-thiodiphenol bis-acylhydrazones were synthesized in good to excellent yields. Initially ethyl-2-chloroacetate was reacted with 4,4′-thiodiphenol, which was further reacted with e...

Citation: Ramos-Inza, S.; Aliaga, C.; Encío, I.; Raza, A.; Sharma, A.K.; Aydillo, C.; Martínez-Sáez, N.; Sanmartín, C.; Plano, D. First Abstract: The introduction of selenium (Se) into organic scaffolds has been demonstrated to be a promising framework in the field of medicinal chemistry. A novel design of nonsteroidal anti-inflammatory drug (NSAID...

James Lovelock's statement that: "We should no longer be talking about the 'sustainable development' of our civilisation, but about 'sustainable retreat', about the radical transformation of habitats, about the possibility of the continuation of bare life." is an important basic idea in ecological architecture. It also highlights the fact that this...

Side chain-fluorinated amino acids are useful tools in medicinal chemistry and protein science. In this review, we outline some general strategies for incorporating fluorine atom(s) into amino acid side chains and for elaborating such building blocks into more complex fluorinated peptides and proteins. We then describe the diverse benefits that flu...

The evolution of bisindolyl maleimides and indolyl maleimide derivatives and their unique biological activities have stimulated great interest in medicinal chemistry programs. Bisindolylmaleimide (BIM)-type compounds arise from natural sources such as arcyriarubin and are biosynthetically related to indolocarbazoles. BIMs are commonly the immediate...

Bioisosteric design has become an essential approach in the development of novel drug molecules. Recent advancements in synthetic methodologies have enabled the rapid adoption of this strategy into drug discovery programs. Consequently, conceptionally innovative practices would be appreciated by the medicinal chemistry community. Here we report an...

Aim. To synthesize new fluoro-containing building blocks for medicinal chemistry purposes using electrophilic reactions of 7-(trifluoromethyl)-2,3-dihydro-1H-pyrrolizine. Results and discussion. Synthetic approaches to 5-halogeno- and 5-acyl-7-(trifluoromethyl)-2,3-dihydro-1H-pyrrolizines have been developed. The obtained new trifluoromethyl-contai...

The introduction of trifluoromethyl groups into organic molecules is of paramount importance in modern synthetic chemistry and medicinal chemistry. While methods for constructing C(sp2)-CF3 bonds have been well established, the advancement of practical and comprehensive approaches for forming C(sp3)-CF3 bonds remains considerably restricted. In thi...

In this study, novel morpholinium chelidamate salts that could be used as drug candidates are synthesised and described. Morpholine and chelidamic acid were used to create the compounds, and their structures were then verified using a variety of spectroscopic methods, including FT-IR, NMR, UV, density functional theory (DFT), and an in-silico ADMET...

Boron Neutron Capture Therapy (BNCT) is a pioneering medical approach seamlessly integrating the precision targeting characteristics intrinsic to chemotherapy with the anatomical localization principles underpinning conventional radiotherapy. A standout feature of BNCT is its exceptional capacity to establish a significant dosage gradient, effectiv...

Efficacy data from diverse chemical libraries, screened against the various stages of the malaria parasite Plasmodium falciparum , including asexual blood stage (ABS) parasites and transmissible gametocytes, serves as a valuable reservoir of information on the chemical space of compounds that are either active (or not) against the parasite. We post...

Dengue (breakbone fever) is a rapidly spreading arboviral infection transmitted by Aedes mosquitoes with major public health implications in more than 100 tropical and subtropical countries mostly in Southeast Asia, South and Central America and the Western Pacific. As the virus spreads to new geographic areas, more frequent dengue outbreaks occur...

Planar chiral ferrocenes are extensively investigated structures in asymmetric catalysis, materials science, and medicinal chemistry. Although the synthetic approaches for six-membered fused planar chiral ferrocenes are well-established, the construction of a seven-membered fused ring via [4+3] annulation has remained unexplored and seems to be cha...

Background: Molecular hybridization and isostery are proven approaches in medicinal chemistry, and as such we used them to design novel compounds that we investigated as potential antimycobacterials to combat drug-resistant strains. Methods & results: Prepared N-alkyl-2-(pyrimidine-5-carbonyl)hydrazine-1-carboxamides were cyclized to N-alkyl-5-(pyr...

Aryl phosphonates are prevalent moieties in medicinal chemistry and agrochemicals. Their chemical synthesis normally relies on the use of precious metals, harsh conditions or aryl halides as substrates. Herein, we describe a sustainable light-promoted and site-selective C-H phosphonation of arenes via thianthrenation and the formation of an electro...

Several fields of modern chemical studies were inspired by and still follow the chemistry of natural substances. New therapeutic choices were made possible in particular by natural chemicals, and the history of medicinal chemistry is full of instances in this regard. Furthermore, modern drug discovery tools can provide natural derivatives a new l...

Dear Colleagues, In the 21st century, the century that makes all dreams come true, medicine will allow us to forget about pain, old age, and diseases. Nothing could be more wrong. Civilization diseases, otherwise known as lifestyle diseases, social diseases, or diseases of the 21st century include noncommunicable diseases that spread around the wo...

The development of environment-friendly new Poly-adenosine diphosphate (ADP)-ribose Polymerase (PARP) inhibitors are highly essential because of their involvement in the survival of cancer cells. Therefore, a library of indazolyl-substituted-1,3,4-oxadiazoles known to inhibit PARP in cancer cells was synthesized by a green protocol. Furthermore, th...

A monitoria de Química Orgânica foi imprescindível durante o ensino remoto e, posteriormente, na adaptação do retorno às atividades presenciais, em razão dos inúmeros desafios de ambas as modalidades. Desse modo, baseando-se no plano de atividades proposto a monitora, foram desenvolvidas listas de exercício dos assuntos abordados, além de plantões...