Field Of Medicinal Chemistry Research Articles

A review on pyrimidine‐based derivatives: Synthesis and their biological application

AbstractPyrimidine‐based derivatives have attracted a lot of interest in heterocyclic chemistry due to its versatile structure and diverse biological activities. This study provides a comprehensive overview of synthetic strategy of different pyrimidine ring and highlights their biological importance. In this article, we start off by going through the fundamental procedures for the synthesis of pyrimidine scaffolds, including both conventional and contemporary synthetic techniques. These works cover a range of therapeutic domains, such as effects that are anticancer, antibacterial, antiviral, anti‐inflammatory, antioxidant, antimalarial, and so on. Moreover, we have summarized with a discussion of future prospects and challenges in the field of pyrimidine heterocyclic chemistry. This thorough review is a significant resource for researchers in medicinal chemistry and related fields since it offers insightful information about the synthetic methods and biological applications of pyrimidine‐based derivatives.

Experimental biological studies of novel tetradentate hydrazone Cu(II) complexes for potential applications in medicinal chemistry

A series of mononuclear Cu(II) complexes were synthesized using a potential tetradentate hydrazone ligand obtained from the reaction between phenylhydrazine groups and 2,5-thiophenedicarboxaldehyde. The structures of ligands and complexes were elucidated through various spectroscopic techniques, confirming their composition. All complexes were found to adopt four-coordinated geometries, indicating the formation of stable structures. Spectroscopic analysis revealed that the hydrazone ligand coordinated with the Cu(II) metal ions as a dibasic tetradentate ligand by utilizing the phenolic oxygen and azomethine nitrogen atoms. The binding affinity of the complexes with calf thymus DNA (CT-DNA) was investigated using absorption and viscosity measurements, demonstrating their interaction through the intercalation mode. The binding studies showed that the Cu(II) complexes exhibited varying degrees of binding affinity, with Cu(L4) demonstrating the highest affinity, followed by Cu(L1), Cu(L2), and Cu(L3). Moreover, the DNA fragmentation properties of the Cu(II) complexes were evaluated, suggesting their potential utilization in pharmaceutical applications. The obtained results highlight the significance of these novel complexes in the field of medicinal chemistry.

Hydrosulfonylation of Alkynes for Stereodivergent Synthesis of Vinyl Sulfones: Synthetic Strategy and Mechanistic Insights.

Direct synthesis of thermodynamically less favorable (Z)-vinyl sulfones presents a notable challenge in organic synthesis. In addition, the development of a stereodivergent synthesis for (E)- and (Z)-vinyl sulfones is crucial but remains elusive. In this study, we present a hydrosulfonylation of aryl-substituted alkynes, achieving a stereodivergent synthesis of (E)- and (Z)-vinyl sulfones by leveraging both thermodynamic and kinetic controls. Notably, the synthesis of challenging (Z)-vinyl sulfones was achieved through a kinetically controlled process without the need for a catalyst. To synthesize (E)-vinyl sulfones, unconventional visible light-mediated isomerization was employed as a means of facilitating the transition to the thermodynamically favored form. The present study encompasses a comprehensive experimental and computational investigation, which provides valuable insights into the reaction mechanism. This investigation reveals two plausible isomerization pathways: a novel double spin-flip mechanism and a hydrogen atom transfer process in the presence of eosin Y. This study not only advances our understanding of isomerization mechanisms beyond conventional energy-transfer routes but also offers a robust and switchable strategy for synthesizing (E)- and (Z)-vinyl sulfones, thereby providing a versatile avenue for the creation of valuable compounds in the fields of organic synthesis and medicinal chemistry.

Recent Advances in Metal-Catalyzed Approaches for the Synthesis of Quinazoline Derivatives.

Quinazolines are an important class of heterocyclic compounds that have proven their significance, especially in the field of organic synthesis and medicinal chemistry because of their wide range of biological and pharmacological properties. Thus, numerous synthetic methods have been developed for the synthesis of quinazolines and their derivatives. This review article briefly outlines the new synthetic methods for compounds containing the quinazoline scaffold employing transition metal-catalyzed reactions.

Multicomponent Click Reaction: An Indispensable Tool for Easy Access of Functionalized 1,2,3‐Triazoles

AbstractMulticomponent reactions are operationally simple and display a significant role in diverse chemical modification by reducing reaction times as well as additional steps involved. In this review, we highlighted the impact of multi‐component reactions in assistance with modular Click chemistry to develop a library of triazole‐appended scaffolds including 1,2,3‐triazole‐fused heterocycles, glycoconjugates, macrocycles as well as in the combinatorial synthesis of differently functionalized triazoles along with mechanistic insights with a diverse range of applications in the field of medicinal chemistry.

Innovative synthesis of drug-like molecules using tetrazole as core building blocks.

Tetrazole is widely utilized as a bioisostere for carboxylic acid in the field of medicinal chemistry and drug development, enhancing the drug-like characteristics of various molecules. Typically, tetrazoles are introduced from their nitrile precursors through late-stage functionalization. In this work, we propose a novel strategy involving the use of diversely protected, unprecedented tetrazole aldehydes as building blocks. This approach facilitates the incorporation of the tetrazole group into multicomponent reactions or other chemistries, aiding in the creation of a variety of complex, drug-like molecules. These innovative tetrazole building blocks are efficiently and directly synthesized using a Passerini three-component reaction (PT-3CR), employing cost-effective and readily available materials. We further showcase the versatility of these new tetrazole building blocks by integrating the tetrazole moiety into various multicomponent reactions (MCRs), which are already significantly employed in drug discovery. This technique represents a unique and complementary method to existing tetrazole synthesis processes. It aims to meet the growing demand for tetrazole-based compound libraries and novel scaffolds, which are challenging to synthesize through other methods.

Novel Azidobenzohydrazide Schiff Bases: Unveiling Effective Synthesis Strategy and Antimicrobial Efficacy Evaluation

AbstractBenzohydrazide analogues are interesting compounds in the field of pharmaceutical, medicinal chemistry, and coordination chemistry, since they are diverse in biological activities, and they are contributing in medicines and drugs. In the present paper, a series of 4‐azido‐N’‐(benzylidene)benzohydrazides have been synthesized with excellent yields via a four steps procedure from amino benzoic acid as the starting substrate. The products have been fully characterized and their antimicrobial activity evaluated by disc diffusion procedure. Notably, such compounds exhibits activity against gram‐positive and gram‐negative bacteria and fungi.

In – Silico Biological Evaluation of Antifungal Drugs - Molinspiration

The aim of this research work is to evaluate In – Silico Antifungal Drugs, in this work Molinspiration is used to provide predictive tools for essential molecular properties, such as lipophilicity, aqueous solubility and pKa, which are critical in drug discovery and cheminformatics. It operates based on a comprehensive database of chemical structures and employs algorithms to calculate these properties. Molinspiration is a renowned software and informatics company that plays a pivotal role in the pharmaceutical and biotechnology industries. With a primary focus on providing cutting-edge cheminformatics tools and software solutions, Molinspiration has significantly contributed to the field of drug discovery and medicinal chemistry. Molinspiration's software is an indispensable resource for the pharmaceutical and biotechnology sectors.

A transformative oxidation process involving silver-based catalysis of para aminobenzyl alcohol for transposing a pollutant into a resource

ABSTRACT A kinetic-spectrophotometric method has been devised to analyze the oxidation reaction of Para-aminobenzyl alcohol [PABAlc] catalyzed by Ag (I). PABAlc is used in numerous fields of pharmaceutical and medicinal chemistry as intermediates. The harmful effects of PABAlc cannot be overlooked in spite of its manifold applications. The toxicity of PABAlc may lead to allergic reactions, serious eye damage, respiratory tract infections amongst few. It became utmost important to formulate a method to establish the presence of PABAlc in a particular sample of water in order to circumvent its proximity to common people. In our work, we have provided an insight to an oxidation process using PABAlc as substrate catalyzed by Ag (I) ions besides proposing a reaction mechanism of the reaction under study with substantial data in the form of different thermodynamic parameters like activation energy (55 kJ/mol−1), temperature coefficient (1.92), enthalpy of activation (52.89 kJ/mol−1), alongside deets related to various effects of oxidant, substrate, catalyst, temperature, pH, ionic strength, and so on, on reaction kinetics. Additionally, the product formed in the proposed mechanism has its commercial importance in the field of pharmacy, dyes, and so on, sufficient enough to put forward a rationale for the investigations.

New 1,3,4‒oxadiazole Quinazolines as Potential Anticancer Agents: Design, Synthesis, Biological Evaluation, and In silico Studies.

A novel series of 1,3,4‒oxadiazole connected to derivatives of quinazolinone (7a-e and 8a-f) was synthesized in the current investigation, and its anticancer and Topoisomerase‒ II inhibitory activity was evaluated. These findings inspired the design, synthesis, and biological analysis of these 1,3,4‒oxadiazole-quinazolinone analogues as antiproliferative Topo‒II inhibitors. The novel compound structures were determined using mass spectrometry and spectral methods (IR, NMR: 1H & 13C). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colourimetric assay has been used to evaluate the anticancer efficacy of these drugs, and Autodock 4.2 provides a description of the docking results. For the more active members, additional biological tests, such as the Topo‒II inhibition experiment, were performed. These compounds' physicochemical and ADMET characteristics were examined in more detail. In the experiment for antiproliferative activity, compounds 7d, 7e, 8c, 8e, and 8f demonstrated encouraging cytotoxicity findings against HCT‒116 and HepG2 cancer cell lines, with IC50 values ranging from 3.85 to 19.43 μM. Compounds 7d, 7e, and 8e were the most potent inhibitors of Topo II with IC50 values of 15.18, 17.55, and 12.59 μM, respectively. Additionally, the docked compound 8c showed the strongest conventional hydrogen bonds among the residues Leu507(B), Asn508(B), Asn520(B), and Glu522(B) in the Human topoisomerase‒IIβ active site in the DNA complex (4G0U) when compared to the findings of docking experiments. New findings have discovered the fact that fused 1,3,4‒oxadiazole bearing quinazolinone contributed great significance in the field of medicinal chemistry due to their diverse biological properties. Finally, the in silico pharmacokinetic profile of all the synthesized derivatives was estimated using SwissADME, where some of the compounds followed Lipinski, Veber, Egan, and Muegge rules without deviation. The result of this activity advises that with a simple modification in structure, a potent anticancer agent can be generated with good efficacy.

Bridged NHC-Pd(II) complexes: Synthesis, DFT calculations, molecular docking, and investigation of catalytic and biological activities

Six palladium(II) (3a-f) complexes of the type [Pd2(μ-Cl)2(NHC)] were prepared by transmetallation of the corresponding Ag-NHC and [PdCl2(CH3CN)2] complexes, and their structures were successfully characterised by 1H NMR, 13C NMR, HRMS, FTIR and elemental analysis. Density functional theory (DFT) calculations were also realised for the complexes. The prepared complexes were assessed for their catalytic activity in the C-H arylation of 2-isobuthylthiazole as well as for their biological activities. As results, these complexes were found to be potent catalysts in the creation of C5-arylated 2-isobuthylthiazole derivatives via C-H bond activation reaction. Furthermore, biological activity analysis revealed that complex 3a exhibits high cytotoxicity towards both human colon carcinoma cell lines (HCT-116) and hepatocellular carcinoma cell lines (HepG-2) with IC50 values of 4.2 and 9.3 µMmL−1, respectively. Complex 3b also showed antioxidant activity comparable to that of BHT through DPPH and ABTS assays. Both complexes 3d and 3f also showed significant inhibitory activity towards the AChE enzyme with IC50 values of 5.06 and 2.52 µMmL−1, respectively. Finally, all complexes showed excellent antiparasitic activity, with 3b exhibiting strong antileishmanial activity against both L. major promastigotes and amastigotes. The interaction between the most cytotoxic complexes and DNA, envisaged as a potential mechanism of toxicity, was explored by means of docking studies. In summary, these prepared complexes have the potential to serve as potent catalysts for the synthesis of arylated 2-isobutylthiazole and biologically active agents, paving the way for numerous prospects in the fields of medicinal chemistry and organic synthesis.

Coumarin-Derived Mannich Bases: A Review of Biological Activities

Abstract: Mannich bases have a distinct place in the field of medicinal and pharmaceutical chemistry. These are used as lead compounds for the synthesis of numerous heterocyclic compounds, which possess diverse biological activities and play pivotal roles. This review covers the latest literature and knowledge on Mannich bases derived from coumarin. In addition, this review also aims to provide a comprehensive overview of recent developments in medicinal chemistry and shed light on the biological activities and structure-activity relationship (SAR) of coumarin-based Mannich bases.

Comprehensive Review on Recent Strategies for Management of Prostate Cancer: Therapeutic Targets and SAR.

Prostate cancer is a disease that is affecting a large population worldwide. Androgen deprivation therapy (ADT) has become a foundation for the treatment of advanced prostate cancer, as used in most clinical settings from neo-adjuvant to metastatic stage. In spite of the success of ADT in managing the disease in the majority of men, hormonal manipulation fails eventually. New molecules are developed for patients with various hormone-refractory diseases. Advancements in molecular oncology have increased understanding of numerous cellular mechanisms which control cell death in the prostate and these insights can lead to the development of more efficacious and tolerable therapies for carcinoma of the prostate. This review is focused on numerous therapies that might be a boon for prostate therapy like signaling inhibitors, vaccines, and inhibitors of androgen receptors. Along with these, various bioactive molecules and their derivatives are highlighted, which act as potential antiprostate cancer agents. This article also emphasized the recent advances in the field of medicinal chemistry of prostate cancer agents.

Rxn-INSIGHT: fast chemical reaction analysis using bond-electron matrices

The challenge of devising pathways for organic synthesis remains a central issue in the field of medicinal chemistry. Over the span of six decades, computer-aided synthesis planning has given rise to a plethora of potent tools for formulating synthetic routes. Nevertheless, a significant expert task still looms: determining the appropriate solvent, catalyst, and reagents when provided with a set of reactants to achieve and optimize the desired product for a specific step in the synthesis process. Typically, chemists identify key functional groups and rings that exert crucial influences at the reaction center, classify reactions into categories, and may assign them names. This research introduces Rxn-INSIGHT, an open-source algorithm based on the bond-electron matrix approach, with the purpose of automating this endeavor. Rxn-INSIGHT not only streamlines the process but also facilitates extensive querying of reaction databases, effectively replicating the thought processes of an organic chemist. The core functions of the algorithm encompass the classification and naming of reactions, extraction of functional groups, rings, and scaffolds from the involved chemical entities. The provision of reaction condition recommendations based on the similarity and prevalence of reactions eventually arises as a side application. The performance of our rule-based model has been rigorously assessed against a carefully curated benchmark dataset, exhibiting an accuracy rate exceeding 90% in reaction classification and surpassing 95% in reaction naming. Notably, it has been discerned that a pivotal factor in selecting analogous reactions lies in the analysis of ring structures participating in the reactions. An examination of ring structures within the USPTO chemical reaction database reveals that with just 35 unique rings, a remarkable 75% of all rings found in nearly 1 million products can be encompassed. Furthermore, Rxn-INSIGHT is proficient in suggesting appropriate choices for solvents, catalysts, and reagents in entirely novel reactions, all within the span of a second, utilizing nothing more than an everyday laptop.

Therapeutic Potential of Natural Metabolites Coupled Pyrazole and Its Bio‐Isosteres: Medicinal Perspectives and SAR Studies

AbstractNatural products have been extensively explored for their role in drug design and development to eradicate numerous types of diseases. Also, heterocycles‐based motifs are known to possess a wide range of therapeutic applications. Among them, pyrazole is a well‐exploited scaffold by researchers in the different fields of medicinal chemistry. Recently, pharmacophoric hybridization became most urged approach in which two biologically active pharmacophoric skeletons tend to fuse together in any structural portion. Hence, pyrazole and its cyclic bio‐isosteres may clubbed together to design and develop novel potent molecules against clinical disorders with least toxicity profile. In the present review, we aim to compile the numerous recent advancements in the medicinal chemistry of natural metabolites containing pyrazole and its bio‐isosteres hybrid compounds with the following objectives: (1) To summarize the recent literature reports of last six years that are focused on the biological potential of natural pyrazole and its bio‐isosteres hybrid derivatives; (2) To deliberate current developments in the medicinal aspect of natural compounds through their structural alteration by introducing pyrazole and its cyclic analogues; (3) To emphasize the complete correlation between structure activity relationship (SAR) and therapeutic response to disclose productive concepts for the generation of potential semi‐synthetic candidates.

The Future of ChatGPT in Medicinal Chemistry: Harnessing AI for Accelerated Drug Discovery

AbstractArtificial Intelligence (AI) has emerged as a transformative tool in various fields, including medicinal chemistry and drug discovery. The integration of artificial intelligence (AI) and machine learning (ML) technologies in medicinal chemistry has revolutionized drug discovery processes. Among AI models, ChatGPT (Generative Pre‐trained Transformer) has shown remarkable capabilities in natural language understanding and generation. This review article delves into the potential applications and prospects of ChatGPT in the domain of medicinal chemistry, focusing on its contributions to drug discovery, compound design, virtual screening, target identification, and optimization of pharmacokinetic properties. ChatGPT′s ability to generate contextually relevant text makes it a valuable tool for data mining and analysis of vast chemical and biological information repositories. In this review article, the authors have discussed the challenges and ethical considerations associated with the implementation of ChatGPT 3.5 in medicinal chemistry research. Authors also extend their acknowledgment to ChatGPT (version 3.5) for its contribution in furnishing responses to the prompt, thereby shedding light on the applications of ChatGPT in the field of medicinal chemistry. The authors have analyzed the responses of ChatGPT.

Exploring 4-chloro chalcone: Synthesis, spectroscopic, chemical reactivity, topological, hirshfeld surface, drug-Likeness, molecular docking and assessment of electronic properties in diverse solvents

Chalcones are a significant class of naturally occurring chemical substances and their derivatives are extremely influential in the field of biological industries. In the current study, the title composite,4 - Chlorochalcone has undergone extensive investigation to understand its spectral properties using a combination of experimental and theoretical calculations. Fourier transform (FT-IR) infrared and FT-Raman characterizations provided valuable insights into the vibrational assignments (functional groups) in the header molecule, while ultraviolet–visible (UV–Vis) spectroscopy explored its electronic transitions and absorbance characteristics. The electronic properties were studied for the solvents viz., ethanol, methanol, DMSO, acetonitrile and benzene through theoretical-computational DFT calculations, revealing details about their molecular orbitals, electronic energies, and other energy parameters. Additionally, the NBO-natural bond orbital analysis shed light on the chemical bonding and electron distributions by donor and acceptor atoms. Furthermore, MEP- molecular electrostatic potential was analyzed for the various solvents and the calculated energy parameters were obtained. A drug-likeness evaluation was performed to assess its potential as a drug candidate based on its molecular properties. Moreover, the topological analysis and electron-hole distributions, contributed to a comprehensive understanding of electron density and localization within the molecule for the solvents viz., ethanol, methanol, DMSO, acetonitrile and benzene. Molecular docking investigations, as well as the Ramchandran plots, revealed that substituents targeting amino acids contribute to the antiviral action of the header compound. The potential of 4′-Chlorochalcone (ligand) as an antiviral agent offers promising prospects for further exploration and development in various therapeutic areas within the field of medicinal chemistry.

Abstract 3542: The Chemical Probes Portal: An essential resource providing expert advice on chemical tools for cancer research

Abstract Background: The Chemical Probes Portal (Portal) serves as a vital resource in the realm of cancer research and biomedical science generally - offering expert guidance on high-quality chemical tools, usually protein inhibitors, crucial for studying physiological and pathological processes and validating therapeutic targets. Researchers often grapple with selecting suitable chemical probes, inadvertently utilizing tools ill-suited for their purpose, and not following best practice, thereby contaminating the scientific literature and wasting valuable time and resources. To address this challenge, the Portal (https://www.chemicalprobes.org) was established as a non-profit, independent online platform, meticulously curating, annotating, and scoring the quality of chemical probes and providing associated information and advice. Results: The Portal stands apart as the sole expert-curated public resource evaluating the quality and utility of small-molecule chemical tool compounds for use in cancer research and wider biomedical research. More than 250 experts, comprising scientific leaders in chemical biology, medicinal chemistry, pharmacology, and related fields, contribute their experience and insights to assess featured chemical probes. Since 2021, a progressively updated and enhanced version of the Portal has been operational, housing over 1000 compounds targeting 500+ proteins across diverse families, now including PROTACs and molecular glues. We also flag 254 ‘Unsuitables’, which are compounds that should not be used to interrogate a specific protein target. Additionally, the Portal now offers informative pages, providing advice delineating guidelines for selecting well-validated compounds, including those suitable for rodent studies, necessitating specific pharmacokinetic and pharmacodynamic properties. Best practice use requires employing high-quality chemical probes from more than one distinct chemical class that target the same protein, incorporating an inactive control compound, and following the recommended concentration range - all aimed at mitigating off-target risks. Conclusion: The enhanced Chemical Probes Portal provides a vital platform for researchers to navigate and evaluate chemical probes, easily and effectively. It employs a rigorous expert review to ensure the quality of the probes listed. The resource not only aids high-quality probe selection but also provides advice through an Information Centre, offering guidelines, FAQs, and additional information on probe criteria and use. The continuous expansion and outreach efforts aim to make the Portal an indispensable tool for cancer researchers and the broader biomedical research community. Researchers are encouraged to participate in the Portal's development and contribute to the robustness of chemical probe use in scientific endeavors. Citation Format: Domenico Sanfelice, Albert Antolin, Alisa Crisp, Yi Chen, Paul Brennan, Susanne Müller, Bissan Al-Lazikani, Aled Edwards, Paul Workman. The Chemical Probes Portal: An essential resource providing expert advice on chemical tools for cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3542.

Bioactive atropisomers: Unraveling design strategies and synthetic routes for drug discovery.

Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field of medicinal chemistry. It has been shown that atropisomers of a wide range of compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal of chirality in atropisomers poses complexity and obstacles in the process of drug discovery and development. Nonetheless, recent progress in understanding atropisomerism and enhanced characterization methods have greatly assisted medicinal chemists in the effective development of atropisomeric drug molecules. This article provides a comprehensive review of their special design thoughts, synthetic routes, and biological activities, serving as a reference for the synthesis and biological evaluation of bioactive atropisomers in the future.

In-vitro Evaluation of Triazine Scaffold for Anticancer Drug Development: A Review.

The widespread importance of the synthesis and modification of anticancer agents has given rise to many numbers of medicinal chemistry programs. In this regard, triazine derivatives have attracted attention due to their remarkable activity against a wide range of cancer cells. This evaluation covers work reports to define the anticancer activity, the most active synthesized compound for the target, the SAR and, when described, the probable MOA besides similarly considered to deliver complete and target-pointed data for the development of types of anti-tumour medicines of triazine derivatives. Triazine scaffold for the development of anticancer analogues. Triazine can also relate to numerous beneficial targets, and their analogues have auspicious in-vitro and in-vivo anti-tumour activity. Fused molecules can improve efficacy, and drug resistance and diminish side effects, and numerous hybrid molecules are beneath diverse stages of clinical trials, so hybrid derivatives of triazine may offer valuable therapeutic involvement for the dealing of tumours. The objective of the recent review was to summarize the recent reports on triazine as well as its analogues with respect to its anticancer therapeutic potential. The content of the review would be helpful to update the researchers working towards the synthesis and designing of new molecules for the treatment of various types of cancer disease with the recent molecules that have been produced from the triazine scaffold. Triazine scaffolds based on 1,3,5-triazine considerably boost molecular diversity levels and enable covering chemical space in key medicinal chemistry fields.