Most Cited Article – Molecular Docking and Pharmacokinetic Studies of Aquillochin and Grewin as SARS-CoV-2 Mpro Inhibitors

Author(s):Adnan Cetin*

Volume 12, Issue 1, 2022

Published on: 10 May, 2022

Page: [54 – 61]

Pages: 8

DOI: 10.2174/2210303112666220318151336


Background: The COVID-19 pandemic emerged at the end of 2019 in China and spread rapidly all over the world. Scientists strive to find virus-specific antivirals against COVID-19 disease. This study aimed to assess bioactive coumarinolignans (Aquillochin, Grewin) as potential SARS-CoV-2 main protease (SARS-CoV-2 Mpro) inhibitors using a molecular docking study.

Methods: The detailed interactions between coumarinolignans and SARS-CoV-2 Mpro were determined as hydrophobic bonds, hydrogen bonds, electronic bonds, inhibition activity, ligand efficiency, bonding type, and distance using Autodock 4.2 software. SARS-CoV-2 Mpro was docked with Aquillochin and Grewin, and the docking results were analyzed by Autodock 4.2 and Biovia Discovery Studio 4.5. Nelfinavir and Lopinavir were used as standards for comparison.

Results: The binding energies of the SARS-CoV-2 Mpro-coumarinolignan’s complexes were identified from the molecular docking of SARS-CoV-2 Mpro. Aquillochin and Grewin were found to be -7.5 and -8.4 kcal/mol, respectively. The binding sites of the coumarinolignans to SARS-CoV-2 Mpro were identified with the main interactions being π-alkyl, alkyl, π-cation, π-π T-Shaped, and hydrogen bonding. Furthermore, SwissADME web tools were used to evaluate ADMET properties and pharmacokinetic parameters of Aquillochin and Grewin. The results of ADMET and pharmacokinetic results of the Aquillochin and Grewin showed that these coumarinolignans were consonant with the many accepted rules and the criteria of drug-likeness.

Conclusion: Aquillochin and Grewin obey Lipinski’s rule of five. According to the results obtained from molecular docking studies and ADMET predictions, Aquillochin and Grewin have shown weak efficacy as drug candidates against COVID-19 disease. Read now:

Testimonial By Sinan Suzen


Read what our Authors have to say about publishing in our Journal

Journal Name: Current Drug Metabolism

Contributed Article:  Volatile Inhibitors of Phosphatidylinositol-3-Kinase (PI3K) Pathway: Anticancer Potential of Aroma Compounds of Plant Essential Oils

Most Accessed Articles | Identification of New Inhibitors of Mutant Isocitrate Dehydrogenase 2 through Molecular Similarity-based Virtual Screening

Journal Name: Letters in Drug Design & Discovery

Author(s): Lijun Yang, Stefan Pusch, Victoria Jennings, Tianfang Ma, Qihua Zhu, Yungen Xu, Andreas von Deimling*, Xiaoming Zha*.





Graphical Abstract:



Background: Isocitrate dehydrogenase 2 (IDH2) is an enzyme catalyzing the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA). Evidences suggest that the specific mutations in IDH2 are critical to the growth and reproduction of severe tumors especially leukemia and glioblastoma. It is found that the inhibitors of mutant IDH2 are promising anti-tumor therapeutics.

Methods: A virtual screening strategy combining molecular similarity search and molecular docking was performed in the binding site of AGI-6780. YL-16, YL-17 and YL-18 were identified as novel mutant IDH2 inhibitors for the reduction of (D)-2-hydroxyglutarate in cellular evaluation. In addition, all the three compounds showed inhibition against IDH2-R172K mutated HEK-293T cells, while weak inhibition against wide-type IDH2 (WT-IDH2) HEK-293T cells.

Results: Significantly, YL-17 showed 84.55% inhibitory activity against IDH2-R172K at 1 µM and weak cytotoxicity to wide-type IDH2 at 50 µM.

Conclusion: YL-17 was highlighted as a new mutant IDH2 inhibitor that could be further developed for therapeutic applications. To read out more, please visit:

Most Cited Articles | Novel Trifluoromethylpyrazole Acyl Thiourea Derivatives: Synthesis, Antifungal Activity and Docking Study

Journal Name: Letters in Drug Design & Discovery

Author(s): Han Wang, Zhi-Wen Zhai, Yan-Xia Shi, Cheng-Xia Tan, Jian-Quan Weng, Liang Han, Bao-Ju Li, Xing-Hai Liu*.





Graphical Abstract:



Background: In recent years, pyrazole carboxamide derivatives possessed excellent fungicidal activity. In the process of designing new fungicides, the carboxamide group was modified in order to find novel structure pyrazole carboxamide derivatives.

Methods: Ten novel trifluoromethyl pyrazole acyl thiourea derivatives were designed and synthesized. In vivo fungicidal activities of these compounds were tested against Fusarium oxysporum, Corynespora mazei and Botrytis cinerea, respectively.

Results: Particularly compounds exhibited significant control effective at 100 mg/L. More importantly, some compounds showed the good control effective at 10 mg/L. Furthermore, docking was established to study the structure-activity relationship of the title compounds.

Conclusion: It is possible that trifluoromethylpyrazole acyl thiurea derivatives, which possess good control effective against Botrytis cinerea, may become novel lead compounds for the development of fungicides with further structure modification. To read out more, please visit:

EDITORS CHOICE ARTICLE – 3D-QSAR Studies of S-DABO Derivatives as Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors

Journal Name: Letters in Drug Design & Discovery

Author(s): Yueping Wang, Jie Chang, Jiangyuan Wang, Peng Zhong, Yufang Zhang, Christopher Cong Lai, Yanping He*.





S-dihydro-alkyloxy-benzyl-oxopyrimidines (S-DABOs) as non-nucleoside reverse transcriptase inhibitors have received considerable attention during the last decade due to their high potency against HIV-1. In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) of a series of S-DABOs analogues developed in our lab was studied using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). Docking simulation based on the co-crystallized complex (PDB ID: 1RT2) were employed to determine the most probable binding mode and to obtain most reliable conformations for molecular alignment. Statistically significant CoMFA (q2=0.766 and r2=0.949) and CoMSIA (q2=0.827 and r2=0.974) models were generated using the training set on the basis of hybrid docking-based and ligand-based alignment. The predictive ability of CoMFA and CoMSIA models were further validated using a test set of eight compounds with predictive r2pred values of 0.843 and 0.723, respectively. The information obtained from the 3D contour maps can be used in designing new S-DABOs derivatives with improved HIV-1 inhibitory activity.



MOST ACCESSED ARTICLE – Natural Product Inhibitors of Topoisomerases: Review and Docking Study

Journal Name: Current Protein & Peptide Science

Author(s): Luciana Scotti*, Francisco Jaime Bezerra Mendonca, Frederico Favaro Ribeiro,Josean Fechine Tavares, Marcelo Sobral da Silva, Jose Maria Barbosa Filho, Marcus Tullius Scotti.



Graphical Abstract:



Since ancient times, natural products have been used in treating various diseases effectively and safely. Nowadays, these natural compounds are submitted to sophisticated methodologies from isolation, computing, analytical, and even serving as pharmacophore suggestions for synthesis. The substances extracted from marine species, plants, and microorganisms present activities beneficial to our health, including protection against malignant tumors. The topoisomerase enzymes play an important role in DNA metabolism, and searching for enzyme inhibitors is an important target in the search for new anticancer drugs. This review discusses this problem, reporting research involving alkaloids, terpenes, flavonoids, xanthones, coumarins, acetogenins, and in addition, includes a docking study with our Brazilian diterpenes to topoisomerases I and II. The better compound, the trachylobane 1, forms one hydrogen bond when submitted to docking with Topo I (with the ASP533 residue) and two with residues in Topo II (THR213 and TYR188). The difference observed in the energy of formation can be attributed to hydrogen-bond interactions.

The difference observed in the energy of formation can be attributed to hydrogen-bond interactions.



HIGHLIGHTED ARTICLE – Decrease in the Generation of Amyloid-β Due to Salvianolic Acid B by Modulating BACE1 Activity – CURRENT ALZHEIMER RESEARCH

CAR-Articles_14-12-Siva Sundara Kumar.jpg

To access the article, please visit:

Highlighted Article – Exploration of Angiotensin II Type 1 Receptor Modulators by Molecular Fingerprints and Docking Simulations – Letters in Drug Design & Discovery

LDDD-Articles_14-12-Sarfaraj Niazi.jpg

To access this article, please visit:

Major Article Contributions by some of the Indian Authors of Bentham Science Publishers in the Journal: Medicinal Chemistry

Journal Name: Medicinal Chemistry

Article Title QSAR Study on a Series of Aryl Carboxylic Acid Amide Derivatives as Potential Inhibitors of Dihydroorotate Dehydrogenase (DHODH)

Author(s): Vivek K. Vyas and Manjunath Ghate

Abstract: QSAR study was performed on a series of aryl carboxylic acid amide derivatives (62 analogs) to establish structural features required for human dihydroorotate dehydrogenase (hDHODH) inhibition. Statistical significant QSAR models were developed for the prediction of hDHODH inhibitory activity by applying MLR analysis (r2 = 0.851 and q2 = 0.795), PCR analysis (r2 = 0.713 and q2 = 0.667) and PLS analysis (r2 = 0.848 and q2 = 0.802). QSAR study emphasized the importance of topological, estate number, hydrophobic and alignment independent descriptors for the prediction of hDHODH inhibitory activity. SaasCcount descriptor suggested the presence of carbon atoms in five member aryl ring system. Positive impact of alignment independent descriptors reveals the presence of carbonyl oxygen and chloro group in this series of compounds. DistTopo signifies basic connectivity of atoms in the molecules. High degree of predictability of the proposed QSAR models offers a great potential for the design and development of potent hDHODH inhibitors.

For more Details, visit:

Article Title: QSAR and Docking Based Semi-synthesis and in vitro Evaluation of 18 β-glycyrrhetinic Acid Derivatives Against Human Lung Cancer Cell Line A-549

Author(s): Dharmendra Kumar Yadav, Komal Kalani, Feroz Khan and Santosh Kumar Srivastava

Abstract: For the prediction of anticancer activity of glycyrrhetinic acid (GA-1) analogs against the human lung cancer cell line (A-549), a QSAR model was developed by forward stepwise multiple linear regression methodology. The regression coefficient (r2) and prediction accuracy (rCV2) of the QSAR model were taken 0.94 and 0.82, respectively in terms of correlation. The QSAR study indicates that the dipole moments, size of smallest ring, amine counts, hydroxyl and nitro functional groups are correlated well with cytotoxic activity. The docking studies showed high binding affinity of the predicted active compounds against the lung cancer target EGFR. These active glycyrrhetinic acid derivatives were then semi-synthesized, characterized and in-vitro tested for anticancer activity. The experimental results were in agreement with the predicted values and the ethyl oxalyl derivative of GA-1 (GA-3) showed equal cytotoxic activity to that of standard anticancer drug paclitaxel.

For more details, visit:

Article Title: Synthesis, Leptospirocidal Activity and QSAR Analysis of Novel Quinoxaline Derivatives

Author(s): Ayarivan Puratchikody, Ramalakshmi Natarajan, Mukesh Doble, Shanmugam Hema Iswarya and Raj Vijayabharathi

Abstract: A simple and efficient method has been developed for the synthesis of series of N-Mannich bases of (E)-3- (phenylimino/4-chlorophenylimino)-2,3-dihydro-1-[(N-substituted piperazinyl) methyl]quinoxaline-2-(1H)-one 3a-f and 4a-f. The requisite 2a and 2b were obtained by reactionbetween quinoxaline-2,3-dione 1 and aniline / p-chloroaniline. These compounds underwent NMannich reaction with various substituted piperazines to yield (title compounds 3a-f and 4a-f respectively. Structures of synthesized compounds were confirmed by spectral studies (IR, 1H NMR, 13C NMR and Mass) and elemental analysis. All the synthesized compounds were screened for in vitro leptospirocidal activty against Leptospira interrogans. The potent compounds 4a, 4b and 4c which showed maximum activity during in vitro studies were subjected to in vivo studies. The inhibitory activity of enzymes carboxypeptidase and transpeptidase, in leptospirosis by the synthesized compounds were determined. 3D-QSAR studies model developed showed the need for more hydrophobic and less steric groups as substituent groups to enhance the in vitro activity.

For more details, Visit:

Major Article Contributions by Some of our Indian Authors in Bentham Science Publishers Journal: Medicinal Chemistry


New Quinolinyl–1,3,4–Oxadiazoles: Synthesis, In Vitro Antibacterial, Antifungal and Antituberculosis Studies

Author(s): Rahul V. Patel, Premlata Kumari and Kishor H. Chikhalia

Affiliation: Department of Applied Chemistry, S. V. National Institute of Technology, Surat–395007, Gujarat, India.


In order to generate hybrid antimicrobial remedies with novel mode of action, two series of quinoline based 1,3,4-oxadiazole derivatives condensed with N-aryl/benzothiazolyl acetamides were synthesized and the MIC values of the compounds towards eight reference bacterial strains (S. aureus, B. cereus, E. coli, P. aeruginosa, K. pneumoniae, S. typhi, P. vulgaris, S. flexneri), four fungi (A. niger, A. fumigatus, A. clavatus, C. albicans) and Mycobacterium tuberculosis H37Rv were assayed in vitro. Quinoline–6–carboxlic acid was treated with thionyl chloride in refluxing methanol to obtain the corresponding ester derivative to be hydrazinolyzed by 99% hydrazine hydrate in ethanol to produce carbohydrazide intermediate. The carbohydrazide precursor underwent cyclization by carbon disulfide and ethanolic KOH to construct 5–quinolinyl–6–yl–1,3,4–oxadiazol–2–thiol. Substituted 2–chloro–N–phenyl(benzothiazolyl)aceta-mide derivatives were then condensed to 1,3,4-oxadiazole nucleus via sulphur linkage to yield the desired products. Target products bearing N–benzothiazolyl–2–chloroacetamides displayed good inhibitory potential. The biological screening identified that many final analogues exhibited a significant inhibition of the growth of microorganisms at 3.12-25 μg/mL of MIC, which were comparable to control drugs. The influence of the presence of various functional groups to the phenyl/benzothiazolyl ring on activity profiles was investigated. The proposed structures of the newly prepared products were confirmed with the aid of IR, 1H NMR, 13C NMR spectroscopy and elemental analysis. These results may provide new insights in the design of a novel pool of bioactive templates.

A Combination of 3D-QSAR Modeling and Molecular Docking Approach for the Discovery of Potential HIF Prolyl Hydroxylase Inhibitors

Author(s): Mahesh Kumar Teli and Rajanikant Golgodu Krishnamurthy

Affiliation: School of Biotechnology Coordinator, Bioinformatics Centre National Institute of Technology Calicut Calicut – 673601, Kerala, India.


Suppression of HIF prolyl hydroxylase (PHD) activity by small molecule inhibitors leads to the stabilization of HIF and offers a potential therapeutic option for treating ischemic disorders. In this study, pharmacophore based QSAR modeling, virtual screening and molecular docking approaches were concurrently used to identify target-specific PHD inhibitors with better ADME properties and to readily minimize false positives and false negatives. A 3D-QSAR based method was used to generate a pharmacophore hypothesis (AAAN). The obtained 3D-QSAR model has an excellent correlation coefficient value (r2 = 0.99), Fisher ratio (F = 386) and exhibited good predictive power (q2 = 0.64). The hypothesis was validated and utilized for chemical database screening and the retrieved compounds were subjected to molecular docking for further refinement. Quantitative AAAN hypothesis comprised three H-bond accepter and one negative ionizable group feature and it give good predictive ability because all the QSAR information it was providing matched with the active site information. The hypothesis was validated and used as a 3D query for database screening. After manual selection, molecular docking and further refinement, based on the molecular interactions of inhibitors with the essential amino acids residues, 12 candidates with good ADME and blood brain barrier permeability values were selected as potential PHD inhibitors.

Modeling of LIM-Kinase 2 Inhibitory Activity of Pyrrolopyrimidine Analogues: Useful in Treatment of Ocular Hypertension and Glaucoma

Author(s): Gagandip Singh, Manish K. Gupta, Viney Kumar and Yenamandra S. Prabhakar

Affiliation: Molecular Modeling and Pharmacoinformatics Lab, Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga-142001, India.


The LIM-Kinase 2 (LIMK2) inhibitory activity of a series of pyrrolopyrimidine analogs has been analyzed through combinatorial protocol in multiple linear regressions (CP-MLR) and partial least square (PLS) using different descriptors obtained from DRAGON software. The empirical, topological and charge descriptors have led to statistically significant QSAR models and showed good external predictivity as reflected in test set R2 values (0.782 to 0.888). The obtained structure-activity correlations underlined the significance of bulkiness and molecular polarizability in improving the activity. The topological descriptors suggested that open chain or branched substituents are favorable while cyclic /ring substituents are unfavorable for the activity. The descriptors identified in the study showed that pyrrolopyrimidine scaffold holds scope for modulating LIMK2 inhibitory activity. The study gives a direction for further exploration of chemical space of pyrrolopyrimidine analogs as LIMK2 inhibitors.

Variable Selection Based QSAR Modeling on Bisphenylbenzimidazole as Inhibitor of HIV-1 Reverse Transcriptase

Author(s): Surendra Kumar and Meena Tiwari

Affiliation: Computer Aided Drug Design Lab, Department of Pharmacy, Shri G. S. Institute of Technology and Science, 23, Park Road, Indore-452003, (M.P.), India.


The emergence of mutant virus in drug therapy for HIV-1 infection has steadily risen in the last decade. Inhibition of reverse transcriptase enzyme has emerged as a novel target for the treatment of HIV infection. The aim to decipher the structural features that interact with receptor, we report a quantitative structure activity relationship (QSAR) study on a dataset of thirty seven compounds belonging to bisphenylbenzimidazoles (BPBIs) as reverse transcriptase inhibitors using enhanced replacement method (ERM), stepwise multiple linear regression (Stepwise-MLR) and genetic function approximation (GFA) method for selecting a subset of relevant descriptors, developing the best multiple linear regression model and defining the QSAR model applicability domain boundaries. The enhanced replacement method was found to give better results r2=0.8542, Q2(loo) = 0.7917, r2pred = 0.7812) at five variables as compared to stepwise MLR and GFA method, evidenced by internal and external validation parameters. The modified r2 (r2m) of the training set, test set and whole data set were calculated and are in agreement with the enhanced replacement method. The results of QSAR study rationalize the structural requirement for optimum binding of ligands. The developed QSAR model shows that hydrophobicity, flexibility, three dimensional surface area, volume and shape of molecule are important parameters to be considered for designing new compounds and to decipher reverse transcriptase enzyme inhibition activity of these compounds at molecular level. The applicability domain was defined to find the similar analogs with better prediction power.

%d bloggers like this: