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Computational Chemistry of Pharmaceutical and Biomolecules

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 11524

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Special Issue Editor

Dr. Sambantham Muthu

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Guest Editor

Department of Physics, Aringnar Anna Government Arts College, Cheyyar-604407, Tamilnadu, India
Interests: computational chemistry; spectroscopy; drug discovery; biomolecules; quantum chemistry; biophysics

Special Issue Information

Dear Colleagues,

The Special Issue of the journal Molecules covers research articles/papers in the following areas.

We promote publications that combine theoretical and experimental approaches. The structural insights gained from the studies should be related to the properties, function and reactivity of the molecule under investigation and the interactions of this molecule and its implications should be discussed.

Drug discovery is a critical issue in pharmaceutical research as it is a very cost-effective and time-consuming process for producing a new drug candidate. There are a number of computational advances which have significant impact in the field of computer-aided drug design over the last several years.

These advances can be grouped into three basic areas: conformational modeling (of small molecules, macromolecules and their complexes), property modeling (of physical, biological and chemical properties) and molecular design (to optimize physical, biological or chemical properties). Hence, computational approaches have provided a tremendous opportunity to pharmaceutical companies to identify new potential drug targets, which in turn affect the success and time of performing clinical trials for discovering new drug targets.

Spectroscopy techniques used to provide a wealth of quantitative and qualitative information on the chemical and physical–chemical properties of molecular systems in a variety of environments. The advances in spectroscopes lie in the development of theory, instruments, spectral analysis and applications. In spectral analysis, the quantum chemical approach is particularly important. It is useful not only for spectral analysis such as band assignments but also for studies of structure, reactions, and physical–chemical properties of molecules.

Theoretical studies may include computer simulations and quantum computational investigations.

Experimental studies may include Spectroscopy (IR, Raman, UV, NMR, ESR, and Mossbauer, etc.), X-ray crystallography, dielectric relaxation, and nonlinear optics.

Other topics within the scope of this Special Issue include:

Determination of molecular structure;
Organic molecules;
Natural, synthesized drug molecules;
Polymers;
Molecular nanotechnology;
Biological active molecules;
Pharmaceutical drug development (small molecules/large molecules);
The biological evaluation of mixture of molecules such as synthesis, purchased compounds, plant extracts with theoretical studies (drug likeness, qualitative structural-activity relationship analysis, ADME/toxicity and molecular docking) and experimental studies, hence their therapeutic potential.

Important note:

Molecules that have already been studied will not be accepted in this journal. Submissions must include a newly discovered molecule and a new kind of work.

Dr. Sambantham Muthu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

computational drug design
bimolecular
spectroscopy
toxicity
molecular structure
molecular docking

Published Papers (6 papers)

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Research

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13 pages, 4117 KiB

Open AccessArticle

Design and Synthesis of D₃R Bitopic Ligands with Flexible Secondary Binding Fragments: Radioligand Binding and Computational Chemistry Studies

by Gui-Long Tian, Chia-Ju Hsieh, Michelle Taylor, Ji Youn Lee, Robert R. Luedtke and Robert H. Mach

Molecules 2024, 29(1), 123; https://doi.org/10.3390/molecules29010123 - 24 Dec 2023

Viewed by 738

Abstract

A series of bitopic ligands based on Fallypride with a flexible secondary binding fragment (SBF) were prepared with the goal of preparing a D₃R-selective compound. The effect of the flexible linker ((R,S)-trans-2a–d), SBFs ((R,S)-trans-2h–j), and the chirality of orthosteric binding fragments (OBFs) ((S,R)-trans-d, (S,R)-trans-i, (S,S)-trans-d, (S,S)-trans-i, (R,R)-trans-d, and (R,R)-trans-i) were evaluated in in vitro binding assays. Computational chemistry studies revealed that the interaction of the fragment binding to the SBF increased the distance between the pyrrolidine nitrogen and ASP110^3.32 of the D₃R, thereby reducing the D₃R affinity to a suboptimal level. Full article

(This article belongs to the Special Issue Computational Chemistry of Pharmaceutical and Biomolecules)

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15 pages, 4721 KiB

Open AccessArticle

Spectroscopic, Spectrometric and Computational Studies of New Lasalocid Derivatives and Their Complexes with Selected Metal Cations

by Monika Papsdorf and Radosław Pankiewicz

Molecules 2023, 28(24), 8085; https://doi.org/10.3390/molecules28248085 - 14 Dec 2023

Viewed by 600

Abstract

A series of five esters of lasalocid with neopentyl alcohol (LasNeo), geraniol (LasGeran), 2-ethylhexanol (LasEtHex), eicosanol (LasEico) and vanillyl alcohol (LasVanil) were synthesized and studied by NMR, FT-IR and ESI-MS. Then, their complexes with lithium, sodium and potassium cations were obtained and examined using FT-IR. The analysis of the products confirmed the synthesis of new esters with good yields. The newly obtained compounds, as well as their complexes with monovalent cations, were proved to be stabilized by a strong system of intramolecular hydrogen bonds. The PM6 semiempirical calculations provided information on the heat of formation (HOF) and permitted the making of visual representations of the structures of the newly synthesized esters and their complexes with the investigated cations. All the computational outcomes were consistent with the spectroscopic data. Full article

(This article belongs to the Special Issue Computational Chemistry of Pharmaceutical and Biomolecules)

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13 pages, 3235 KiB

Open AccessArticle

Identification of Small Molecule Inhibitors of Human Cytomegalovirus pUL89 Endonuclease Using Integrated Computational Approaches

by Mazen Almehmadi, Ihtisham Ul Haq, Ahad Amer Alsaiari, Fahad M. Alshabrmi, Osama Abdulaziz, Mamdouh Allahyani, Mohammed Aladhadh, Alaa Shafie, Abdulelah Aljuaid, Rema Turki Alotaibi, Jawad Ullah and Nada Saud Alharthi

Molecules 2023, 28(9), 3938; https://doi.org/10.3390/molecules28093938 - 7 May 2023

Viewed by 1889

Abstract

Replication of Human Cytomegalovirus (HCMV) requires the presence of a metal-dependent endonuclease at the C-terminus of pUL89, in order to properly pack and cleave the viral genome. Therefore, pUL89 is an attractive target to design anti-CMV intervention. Herein, we used integrated structure-based and ligand-based virtual screening approaches in combination with MD simulation for the identification of potential metal binding small molecule antagonist of pUL89. In this regard, the essential chemical features needed for the inhibition of pUL89 endonuclease domain were defined and used as a 3D query to search chemical compounds from ZINC and ChEMBL database. Thereafter, the molecular docking and ligand-based shape screening were used to narrow down the compounds based on previously identified pUL89 antagonists. The selected virtual hits were further subjected to MD simulation to determine the intrinsic and ligand-induced flexibility of pUL89. The predicted binding modes showed that the compounds reside well in the binding site of endonuclease domain by chelating with the metal ions and crucial residues. Taken in concert, the in silico investigation led to the identification of potential pUL89 antagonists. This study provided promising starting point for further in vitro and in vivo studies. Full article

(This article belongs to the Special Issue Computational Chemistry of Pharmaceutical and Biomolecules)

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21 pages, 5874 KiB

Open AccessArticle

Discovery of Pyrimidine- and Coumarin-Linked Hybrid Molecules as Inducers of JNK Phosphorylation through ROS Generation in Breast Cancer Cells

by Na Young Kim, Divakar Vishwanath, Zhang Xi, Omantheswara Nagaraja, Ananda Swamynayaka, Keshav Kumar Harish, Shreeja Basappa, Mahendra Madegowda, Vijay Pandey, Gautam Sethi, Peter E. Lobie, Kwang Seok Ahn and Basappa Basappa

Molecules 2023, 28(8), 3450; https://doi.org/10.3390/molecules28083450 - 13 Apr 2023

Cited by 6 | Viewed by 1771

Abstract

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer exhibits early relapses, poor prognoses, and high recurrence rates. Herein, a JNK-targeting compound has been developed that may be of utility in HER2-positive mammary carcinoma. The design of a pyrimidine-and coumarin-linked structure targeting JNK was explored and the lead structure PC-12 [4-(3-((2-((4-chlorobenzyl)thio) pyrimidin-4-yl)oxy)propoxy)-6-fluoro-2H-chromen-2-one (5d)] was observed to selectively inhibit the proliferation of HER2-positive BC cells. The compound PC-12 exerted DNA damage and induced apoptosis in HER-2 positive BC cells more significantly compared to HER-2 negative BC cells. PC-12 induced PARP cleavage and down-regulated the expression of IAP-1, BCL-2, SURVIVIN, and CYCLIN D1 in BC cells. In silico and theoretical calculations showed that PC-12 could interact with JNK, and in vitro studies demonstrated that it enhanced JNK phosphorylation through ROS generation. Overall, these findings will assist the discovery of new compounds targeting JNK for use in HER2-positive BC cells. Full article

(This article belongs to the Special Issue Computational Chemistry of Pharmaceutical and Biomolecules)

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37 pages, 11129 KiB

Open AccessArticle

Elucidating the Role of Noncovalent Interactions in Favipiravir, a Drug Active against Various Human RNA Viruses; a ¹H-¹⁴N NQDR/Periodic DFT/QTAIM/RDS/3D Hirshfeld Surfaces Combined Study

by Jolanta Natalia Latosińska, Magdalena Latosińska, Janez Seliger, Veselko Žagar, Tomaž Apih and Paweł Grieb

Molecules 2023, 28(8), 3308; https://doi.org/10.3390/molecules28083308 - 7 Apr 2023

Cited by 5 | Viewed by 2270

Abstract

Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, FPV), an active pharmaceutical component of the drug discovered and registered in March 2014 in Japan under the name Avigan, with an indication for pandemic influenza, has been studied. The study of this compound was prompted by the idea that effective processes of recognition and binding of FPV to the nucleic acid are affected predominantly by the propensity to form intra- and intermolecular interactions. Three nuclear quadrupole resonance experimental techniques, namely ¹H-¹⁴N cross-relaxation, multiple frequency sweeps, and two-frequency irradiation, followed by solid-state computational modelling (density functional theory supplemented by the quantum theory of atoms in molecules, 3D Hirshfeld Surfaces, and reduced density gradient) approaches were applied. The complete NQR spectrum consisting of nine lines indicating the presence of three chemically inequivalent nitrogen sites in the FPV molecule was detected, and the assignment of lines to particular sites was performed. The description of the nearest vicinity of all three nitrogen atoms was used to characterize the nature of the intermolecular interactions from the perspective of the local single atoms and to draw some conclusions on the nature of the interactions required for effective recognition and binding. The propensity to form the electrostatic N−H···O, N−H···N, and C−H···O intermolecular hydrogen bonds competitive with two intramolecular hydrogen bonds, strong O−H···O and very weak N−H···N, closing the 5-member ring and stiffening the structure, as well as π···π and F···F dispersive interactions, were analysed in detail. The hypothesis regarding the similarity of the interaction pattern in the solid and the RNA template was verified. It was discovered that the -NH₂ group in the crystal participates in intermolecular hydrogen bonds N–H···N and N–H···O, in the precatalytic state only in N–H···O, while in the active state in N–H···N and N–H···O hydrogen bonds, which is of importance to link FVP to the RNA template. Our study elucidates the binding modes of FVP (in crystal, precatalytic, and active forms) in detail and should guide the design of more potent analogues targeting SARS-CoV-2. Strong direct binding of FVP-RTP to both the active site and cofactor discovered by us suggests a possible alternative, allosteric mechanism of FVP action, which may explain the scattering of the results of clinical trials or the synergistic effect observed in combined treatment against SARS-CoV-2. Full article

(This article belongs to the Special Issue Computational Chemistry of Pharmaceutical and Biomolecules)

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Review

Jump to: Research

21 pages, 3169 KiB

Open AccessReview

Halogen-Doped Carbon Dots: Synthesis, Application, and Prospects

by Kun Luo, Yanmei Wen and Xinhuang Kang

Molecules 2022, 27(14), 4620; https://doi.org/10.3390/molecules27144620 - 20 Jul 2022

Cited by 22 | Viewed by 3160

Abstract

Carbon dots (CDs) have many advantages, such as tunable photoluminescence, large two-photon absorption cross-sections, easy functionalization, low toxicity, chemical inertness, good dispersion, and biocompatibility. Halogen doping further improves the optical and physicochemical properties of CDs, extending their applications in fluorescence sensors, biomedicine, photocatalysis, anti-counterfeiting encryption, and light-emitting diodes. This review briefly describes the preparation of CDs via the “top-down” and “bottom-up” approaches and discusses the preparation methods and applications of halogen (fluorine, chlorine, bromine, and iodine)-doped CDs. The main challenges of CDs in the future are the elucidation of the luminescence mechanism, fine doping with elements (proportion, position, etc.), and their incorporation in practical devices. Full article

(This article belongs to the Special Issue Computational Chemistry of Pharmaceutical and Biomolecules)

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