Designing Next-Generation Drug-like Molecules for Medicinal Applications

Khan, Imtiaz; Zaib, Sumera

doi:10.3390/molecules28041860

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…Compounds exhibiting drug-like molecule characteristics are predicted to induce biological activity and possess the ability to penetrate the cell membrane, reaching targets within the cytoplasmic environment. 31 Molecular docking aims to identify how ligands interact with the target domain. 32 In this study, grid docking is used with the position set at Center (Å) X: 2.746, Y: -25.031, Z: 16.706, Dimensions (Å) X: 105.798, Y: 83.933, Z: 106.561 to orient the ligand on the target.…”

Section: Discussionmentioning

confidence: 99%

Antiretroviral activity from elderberry (Sambucus nigra L.) flowers against HIV-2 infection via reverse transcriptase inhibition: a viroinformatics study

Zainul,

Kharisma,

Ciuputri

et al. 2024

Healthc Low-resour S

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HIV-2 infection is a unique concern with fewer cases than HIV-1, but it poses a high mortality rate due to its resistance to all HIV-1 antiretroviral treatments. This study focuses on one type of antiretroviral, reverse transcriptase (RT) inhibitors, as they play an important role in HIV-2 replication. The screening of potential HIV-2 antiretroviral candidates was carried out using compounds from elderberry (Sambucus nigra L.) flower extract. There is a lack of research on the antiviral potential of elderberry flower extracts, particularly in HIV-2; therefore, this study is important to explain the molecular mechanism underlying the potential of elderberry (Sambucus nigra L.) flower extracts to inhibit RT activity in HIV-2 through bioinformatics simulations. This study uses the in silico method, involving sample preparation in the database, drug-like molecular prediction through the server, molecular docking simulation, chemical bond interaction analysis, and three-dimensional structure visualization. Isorhamnetin has the most negative binding affinity of -9.9 kcal/mol compared to other compounds. It interacts with the HIV-2 RT domain at residues Trp4(B), Pro25(B), Asn137(B), Pro133(B), Gln23(B), Pro140(B), Leu21(B), Ile90(A), Thr131(B), Asn57(B), Arg22(B), and Glu89(A) with hydrophobic bond interactions. Hydrogen bond interactions are formed at the positions of Ser134(B), Gly141(B), and Thr88(A). Isorhamnetin from elderberry (Sambucus nigra L.) flower extract could be a potential HIV-2 antiretroviral candidate because it has the most negative binding affinity and the formation of hydrophobic hydrogen bond interactions on the RT domain.

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Section: Discussionmentioning

confidence: 99%

Antiretroviral activity from elderberry (Sambucus nigra L.) flowers against HIV-2 infection via reverse transcriptase inhibition: a viroinformatics study

Zainul,

Kharisma,

Ciuputri

et al. 2024

Healthc Low-resour S

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“…The similarity of query ligands with drug molecules in terms of several druglikeness rules such as Lipinski, Ghose, Veber, Egan, and Muegge was analyzed with Canonical SMILES input from garcinoxanthone, mangostin, and garcinone derivative compounds [34][35][36]. The results of the druglikeness analysis show that all query compounds from Garcinia mangostana L. are probable drug-like molecules because they fulfill at least 3 druglikeness rules such as Lipinski, Ghose, Veber, and Egan.…”

Section: Druglike Compoundsmentioning

confidence: 99%

Bioinformatics study of selective inhibitor from Garcinia mangostana L. tackle HIV‑1 infection

Kharisma,

Ansori,

Jakhmola

et al. 2024

Food systems

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HIV has a host cell, T‑cell lymphocytes with CD4+ receptors. HIV drugs have the inhibitory activity on HIV‑1 protease by producing chemical bonding interactions such as hydrogen and hydrophobic. However, some cases show long-term side effects that may be harmful from the use of synthetic antiretrovirals. This requires new innovations to make drugs based on natural resources or alternative medicine for handling these cases. Natural-based drugs are claimed to reduce the side effects produced. Garcinia mangostana L. or queen of fruit is widely found in Southeast Asia. Many parts of this plant, such as fruits, are used for traditional medicine. Research with in vitro and in vivo approaches reveals that mangostin compounds from Garcinia mangostana L. can be an antiviral candidate. Garcinia mangostana L. has the main chemical compounds of garciniaxanthone, garcinone A, and mangostin. This study uses garciniaxanthone, garcinone A, and mangostin compounds to reveal the molecular mechanism of the antiviral activity in Garcinia mangostana L. through inhibition of HIV‑1 protease with a bioinformatics approach. In silico methods used in this study are druglikeness, molecular docking, interactions, visualization, and dynamic simulation. Garciniaxanthon B, garcinone B, and beta-mangostin from Garcinia mangostana L. have potential as antiretroviral agents for the treatment of HIV‑1 infection. The three compounds are predicted to inhibit the protease activity in HIV‑1 with a more negative binding affinity score, form ligand-protein molecular complexes with van der Waals, hydrogen, pi/alkyl/anion/ sigma bonds, form stable bonds and drug-like molecules.

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Designing Next-Generation Drug-like Molecules for Medicinal Applications

Abstract: The development of new drugs/drug candidates for medical treatment remains an exciting but challenging process as only a limited number of synthetic compounds fit well into the discovery and development process after multiple experiments and screening for their preclinical properties [...]

Cited by 2 publications

References 17 publications

Antiretroviral activity from elderberry (<i>Sambucus nigra</i> L.) flowers against HIV-2 infection via reverse transcriptase inhibition: a viroinformatics study

Antiretroviral activity from elderberry (<i>Sambucus nigra</i> L.) flowers against HIV-2 infection via reverse transcriptase inhibition: a viroinformatics study

Bioinformatics study of selective inhibitor from <i>Garcinia mangostana</i> L. tackle HIV‑1 infection

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