QSAR Modeling of Aminopeptidase N/CD13 (APN) Inhibitory Activity of some Leucine Ureido Derivatives by GA-MLR and SW-MLR Methods

Faraji, Naser; Zebardast, Tannaz; Zarghi, Afshin; Hajimahdi, Zahra

doi:10.2174/1570180814666170529084557

Cited by 2 publications

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“…While overviewing the previously performed QSAR studies [60][61][62][63][64][65][66][67][68][69], it is observed that there are a few common features present namely electronegative and electropositive substitutions, hydrophobicity, steric properties, molecular symmetry, atomic masses and hydrogen bond donor-acceptor features which are responsible for the fluctuation in the potency of the APN inhibitors. Our previous study on 175 diverse set of APN inhibitors [63] disclosed that a few molecular features of the APN inhibitors namely the positive ionizable, hydrogen bond donor-acceptor and ring aromatic features of molecules are some of the important molecular features have important roles in determining the APN inhibitory activity of these molecules [63].…”

Section: Comparison Of the Previously Performed Qsar Studies With Thementioning

confidence: 99%

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Banerjee

Amin

Baidya

et al. 2020

SAR and QSAR in Environmental Research

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The zinc-dependent enzyme aminopeptidase N (APN) is a member of the M1 metalloenzyme family. The multi-functionality of APN as a peptidase, a receptor and a signalling molecule has provided it the access to influence a number of disease conditions namely viral diseases, angiogenesis, cellular metastasis and invasion including different cancer conditions. Hence, the development of potent APN inhibitors is a possible route for the treatment of diseases related to the activity of APN. In this study, different QSAR approaches have been adopted to identify the structural features of a group of hydroxamate-based ureido-amino acid derivative APN inhibitors. This study was able to identify different constitutional aspects of these APN inhibitors which are important for their inhibitory potency. Additionally, some of these observations were also aligned with the observations of previously performed QSAR studies conducted on different APN inhibitors. Therefore, the results of this study may help to design potent and effective APN inhibitors in the future. ARTICLE HISTORY

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Section: Comparison Of the Previously Performed Qsar Studies With Thementioning

confidence: 99%

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Banerjee

Amin

Baidya

et al. 2020

SAR and QSAR in Environmental Research

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Design, Synthesis, Molecular Modeling and Anti-HIV Assay of Novel Quinazolinone Incorporated Coumarin Derivatives

Safakish

Hajimahdi

Aghasadeghi

et al. 2020

CHR

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Background: The emergence of drug-resistant viral strains has created the need for the development of novel anti-HIV agents with a diverse structure that targets key enzymes in the HIV lifecycle. Objective: Considering the pharmacophore of integrase inhibitors, one of the validated targets for anti-HIV therapy, we designed a quinazolinone incorporated coumarin scaffold to affect HIV. Method: Coumarin is a beta enol ester and also a well-known drug scaffold. Designed structures were prepared using a one-pot three-compo Results: In vitro anti-HIV and cytotoxicity assay indicated that more than half of the compounds had EC50 values lower than 50 µM. Unsubstituted phenyl derivative showed the highest activity and selectivity with an EC50 value of 5 µM and a therapeutic index of 7. Compounds were docked into the integrase active site to investigate the probable mechanism of action. Accordingly, the hydroxyl moiety of coumarin along with the carbonyl of the quinazolinone ring could function as the metal chelating group. Quinazolinone and phenyl groups interact with side chains of IN residues, as well. Conclusion: Here, a novel anti-HIV scaffold is represented for further modification and in-vivo studies.

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QSAR Modeling of Aminopeptidase N/CD13 (APN) Inhibitory Activity of some Leucine Ureido Derivatives by GA-MLR and SW-MLR Methods

Cited by 2 publications

References 0 publications

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Design, Synthesis, Molecular Modeling and Anti-HIV Assay of Novel Quinazolinone Incorporated Coumarin Derivatives

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