3D-QSAR Studies Research Articles

Novel antiproliferative inhibitors from salicylamide derivatives with dipeptide moieties using 3D-QSAR, molecular docking, molecular dynamic simulation and ADMET studies

Currently, most cancers cannot be cured permanently. Therefore, the search of new anticancer drugs is an urgent unmet need. In order to solve this problem, we can use computational chemistry as it represents a sensitive step in the procedure of rational drugs development and design. For this study, we performed several in silico approaches such as: 3D QSAR study, molecular docking and molecular dynamics simulation for a database forming of 28 salicylamide compounds with dipeptide moieties that are inhibitors of antiproliferative activity on CEM cancer cell lines. The established CoMSIA/SH model showed a high reliability reflected by an important value of the coefficient of determination (R2 = 0.969), and a reasonable value of the cross-validation coefficient Q² = 0.637, the validity of this model is ensured by the high value of the prediction coefficient for the test set with R2pred = 0.913. The treatment of the different extracted results provides important information about the structures favored to improve the inhibitory activity. These results have guided to propose new antiproliferative inhibitors with high pGI50 values. Subsequently, these new compounds were analyzed using a molecular docking for determine the essential ligand-receptor interactions, then we performed a molecular dynamics simulation that showed the stability of the proposed new compounds, since no significant fluctuation is detected in these validity parameters, finally, to test the possibility of these new inhibitors to become drug candidates we used the ADMET properties.

Structural Insights on Hyp-Gly-Containing Peptides as Antiplatelet Compounds through Topomer CoMFA and CoMSIA Analysis

Increasing evidence has shown collagen hydrolysate involves a variety of bioactivities. In our previous study, multiple antiplatelet peptides containing Hyp/Pro-Gly were identified in collagen hydrolysates from Salmo salar and silver carp skin and exhibited anti-thrombosis activity without bleeding risks in vivo. However, the relationship between structure and activity remains unknown. We performed 3D-QSAR studies on 23 Hyp/Pro-Gly-containing peptides in which 13 peptides were reported before. CoMFA, Topomer CoMFA and CoMSIA analyses were used to generate the QSAR models. Topomer CoMFA analysis showed a q2 value of 0.710, an r2 value of 0.826, an r2pred value of 0.930, and the results showed that Hyp instead of Pro was more important for improving the antiplatelet activity. CoMSIA analysis showed a q2 value of 0.461, an r2 value of 0.999, and an r2pred value of 0.999. Compared with the electrostatic field and hydrogen bond donor field, the steric field, hydrophobic field and hydrogen bond receptor field have great influence on the activity of antiplatelet peptides. The predicted peptide EOGE exhibited antiplatelet activity induced by ADP, and inhibited thrombus formation (300 μmol/kg bw) without bleeding risks. Combined results of these studies indicate that OG-containing peptides had a potential to be developed into an effective specific medical food in the prevention of thrombotic diseases.

Molecular docking, 3D-QSAR and simulation studies for identifying pharmacophoric features of indole derivatives as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5) inhibitors

Excess of androgens leads to various diseases such as Poly-Cystic Ovarian Syndrome, Prostate Cancer, Hirsutism, Obesity and Acne. 17β-Hydroxysteroid Dehydrogenase type 5 (17β-HSD5) converts androstenedione into testosterone peripherally, thereby significantly contributing to the development of these diseases. Indole-bearing scaffolds are reported as potential 17β-HSD5 inhibitors for the manifestation of diseases arising due to androgen excess. In the present work, we have extensively performed a combination of molecular docking, Gaussian field-based 3D-QSAR, Pharmacophore mapping and MD-simulation studies (100 ns) to identify the pharmacophoric features of indole-based compounds as potent 17β-HSD5 inhibitors. Molecular simulation studies of the most potent compound in the binding pocket of enzyme revealed that the compound 11 was stable in the binding pocket and showed good binding affinity through interactions with various residues of active site pocket. The Molecular mechanics Generalized Born surface area continuum solvation (MM/GBSA) and Molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations revealed that the compound 11 possessed a free binding energy of −36.36 kcal/mol and −7.00 kcal/mol, respectively, which was better as compared to reference compound Desmethyl indomethacin (DES). The developed pharmacophore will be helpful to design novel indole-based molecules as potent 17β-HSD5 inhibitors for the treatment of various androgenic disorders. Communicated by Ramaswamy H. Sarma

β-Carboline alkaloids from Picrasma quassioides and their 3D-QSAR study on anti-inflammation in LPS-induced RAW 264.7 cells

Two new β-carboline alkaloids (1–2), 1-pyrrolidone propionyl-β-carboline (1) and 1-(3-hydroxy-2-oxopiperidine-1-ethyl)-4,8-dimethoxyl-β-carboline (2), named kumujantine W and J respectively, together with ten known compounds (3−12) were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were elucidated from spectral data including 1D and 2D NMR, UV, IR, HR-ESI-MS spectroscopic analysis and ECD calculations as well as by comparison to the reference databases or literature. The anti-inflammatory effects of these alkaloids (1−12) and six other β-carboline alkaloids (13–18) in LPS-induced RAW 264.7 cells were evaluated by measuring nitric oxide (NO) concentrations. Among them, compounds 1, 3, 6, 15, and 17 could inhibit the secretion of NO, displaying significant anti-inflammatory activity without affecting cell viability in vitro, and 3D-QSAR analysis further revealed the influence of groups on the activity in β-carboline alkaloids.

3D QSAR Studies of 3, 16 and 17 Position Modifications in Steroidal Derivatives for CNS Anticancer Activity

3D QSAR Studies of 3, 16 and 17 Position Modifications in Steroidal Derivatives for CNS Anticancer Activity

3D-QSAR Studies, Molecular Docking, Molecular Dynamic Simulation, and ADMET Proprieties of Novel Pteridinone Derivatives as PLK1 Inhibitors for the Treatment of Prostate Cancer.

Overexpression of polo-like kinase 1 (PLK1) has been found in many different types of cancers. With its essential role in cell proliferation, PLK1 has been determined to be a broad-spectrum anti-cancer target. In this study, 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations were applied on a series of novel pteridinone derivatives as PLK1 inhibitors to discover anti-cancer drug candidates. In this work, three models-CoMFA (Q² = 0.67, R² = 0.992), CoMSIA/SHE (Q² = 0.69, R² = 0.974), and CoMSIA/SEAH (Q² = 0.66, R² = 0.975)-of pteridinone derivatives were established. The three models that were established gave Rpred2 = 0.683, Rpred 2= 0.758, and Rpred 2= 0.767, respectively. Thus, the predictive abilities of the three proposed models were successfully evaluated. The relations between the different champs and activities were well-demonstrated by the contour chart of the CoMFA and CoMSIA/SEAH models. The results of molecular docking indicated that residues R136, R57, Y133, L69, L82, and Y139 were the active sites of the PLK1 protein (PDB code: 2RKU), in which the more active ligands can inhibit the enzyme of PLK1. The results of the molecular dynamic MD simulation diagram were obtained to reinforce the previous molecular docking results, which showed that both inhibitors remained stable in the active sites of the PLK1 protein (PDB code: 2RKU) for 50 ns. Finally, a check of the ADME-Tox properties of the two most active molecules showed that molecular N° 28 could represent a good drug candidate for the therapy of prostate cancer diseases.

3D-QSAR studies on the structure-bitterness analysis of citrus flavonoids.

Despite their important bioactivities, the unpleasant bitter taste of citrus derived flavonoids limits their applications in the food industry, and the structure-bitterness relationship of flavonoids is still far from clear. In this study, 26 flavonoids were characterized by their bitterness threshold and their common skeleton using sensory evaluation and molecular superposition, respectively. The quantitative conformational relationship of the structure-bitterness of flavonoids was explored using 3D-QSAR based on comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). The results showed that increases of a hydrogen bond donor at A-5 or B-3', a bulky group at A-8, or an electron-withdrawing group at B-4' would enhance the bitterness of flavonoids. The bitterness of some flavonoids was predicted and evaluated, and the results were similar to the bitter intensity of the counterparts from the 3D-QSAR and contour plots, confirming the validation of 3D-QSAR. This study explains the theory of the structure-bitterness relationship of flavonoids, by showing potential information for understanding the bitterness in citrus flavonoids and developing a debittering process.

Aminoquinoline Analogues as Potent Inhibitors of Mycobacterial DNA-GyraseB: 2D and 3D-QSAR Studies

Aminoquinoline Analogues as Potent Inhibitors of Mycobacterial DNA-GyraseB: 2D and 3D-QSAR Studies

Ligand-based Pharmacophore Modeling, Molecular Docking and Simulation Studies for the Exploration of Natural Potent Antiangiogenic Inhibitors Targeting Heat Shock Protein 90

Background: HSP90, a critical molecular chaperone, has become a promising molecular target to be involved in multiple signaling pathways of tumor progression and metastasis. Objective: This study intends to find a novel phytolead targeting HSP90. Methods: In this scenario, we employed an in silico combinatorial approach incorporating 3D-QSAR, pharmacophore generation, pharmacokinetics, docking, MD simulation and metabolism studies. Results: To find a natural novel compound targeting HSP90, a ligand-based pharmacophore model was developed, exploiting 17 diversely classified training set molecules with known experimental activity exhausting the pharmacophore generation (HypoGen algorithm) module of Discovery Studio. The bestdeveloped hypothesis (Hypo1) was employed against the UNPD database to screen lead compounds targeting HSP90. Pterodontoside G (Asteraceae family)became a potent compound with the fit value of 8.80 and an estimated activity of 3.28 nM. Pterodontoside G was taken forward for analog design and pharmacokinetics studies, followed by docking and MD simulation studies. UNPD1 came out to be the best analog following all pharmacokinetics properties with the highest binding energy in comparison with the parent compound and the standard drug (Ganetespib). It mapped all the features of Hypo1 with a fit value of 8.68 and an estimated activity of 4.314 nM, exhibiting greater binding stability inside the active site of HSP90 causing no conformational changes in the protein-ligand complex during MD analysis. Conclusion: The result was further supported by PASS analysis and xenosite reactivity data proposing UNPD1 to hold potent antiangiogenic potential targeting HSP90.

In silico studies of a novel scaffold of benzoxazole derivatives as anticancer agents by 3D-QSAR, molecular docking and molecular dynamics simulations.

The vascular endothelial growth factor receptor-2 kinases (VEGFR-2) expressed on tumor cells and vessels are attractive targets for cancer treatment. Potent inhibitors for the VEGFR-2 receptor are novel strategies to develop anti-cancer drugs. In this work, template ligand-based 3D-QSAR studies were performed on a series of benzoxazole derivatives toward different cell lines (HepG2, HCT-116 and MCF-7). Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques were used to generate 3D-QSAR models. Good predictability was derived for the optimal CoMFA models (HepG2: Rcv2 = 0.509, Rpred2 = 0.5128; HCT-116: Rcv2 = 0.574, Rpred2 = 0.5597; MCF-7: Rcv2 = 0.568, Rpred2 = 0.5057) and CoMSIA models (HepG2: Rcv2 = 0.711, Rpred2 = 0.6198; HCT-116: Rcv2 = 0.531, Rpred2 = 0.5804; MCF-7: Rcv2 = 0.669, Rpred2 = 0.6577). In addition, the contour maps derived from CoMFA and CoMSIA models were also generated to illustrate the relationship between different fields and the inhibitory activities. Moreover, molecular docking and molecular dynamics (MD) simulations were also conducted to understand the binding modes and the potential interactions between the receptor and the inhibitors. Some key residues (Leu35, Val43, Lys63, Leu84, Gly117, Leu180 and Asp191) were pointed out for stabilizing the inhibitors in the binding pocket. The binding free energies for the inhibitors agreed well with the experimental inhibitory activity and indicated that steric, electrostatic and hydrogen bond interactions are the main driving force for inhibitor-receptor binding. Overall, a good consistency between theoretical 3D-SQAR and molecular docking and MD simulation studies would provide directions for the design of new candidates, avoiding time-consuming and costly synthesis and biological evaluations. On the whole, the results derived from this study could expand the understanding of benzoxazole derivatives as anticancer agents and would be of great help in lead optimization for early drug discovery of highly potent anticancer activity targeting VEGFR-2.

Isolation, bioassay and 3D-QSAR analysis of 8-isopentenyl flavonoids from Epimedium sagittatum maxim. as PDE5A inhibitors

BackgroundAs known, inhibition of phosphodiesterase 5 (PDE5) has the therapeutic effect on male erectile dysfunction (ED), and the processed folium of Epimedium sagittatum Maxim. (PFES) characterized by 8-isopentenyl flavonoids is a famous herb for treating ED. However, the main flavonoids inhibitory activities, structure–activity relationship (SAR) and signaling pathway have been not systematically studied so that its pharmacodynamic mechanism is unclear.MethodsWe aimed to initially reveal the PFES efficacy mechanism for treating ED. For the first time, 6 main 8-isopentenyl flavonoids (1–6) from PFES were isolated and identified. Then based on HPLC detection, we proposed a novel method to screen inhibitors among them. We further analyze the three-dimensional quantitative structure–activity relationship (3D-QSAR) for those inhibitors.ResultsThe results were verified by cellular effects of the screened flavonoids. Among 6 compounds, Icariin: (1), 2-Oʹʹrhamnosylicaridide II (2) and Baohuoside I (3) were identified with significant activities (IC50 = 8.275, 3.233, 5.473 μM). Then 3D-QSAR studies showed that the replacement of C8 with bulky steric groups as isopentenyl, C3 with positive charge groups and C4' with a hydrogen bond acceptor substituent could increase inhibitory effects. In contrast, the substitution of C7 with bulky steric groups or hydrophilic groups tended to decrease the efficacies. And compounds 1, 2, 3 could increase cGMP level and decrease cytoplasmic Ca2+ of rat corpus cavernosum smooth muscle cells (CCSMCs)by activating PKG.Conclusion8-isopentenyl flavonoids could be the main pharmacodynamic substances of PFES in the treatment for ED, and some had significant PDE5A1 inhibitory activities so as to activate cGMP/PKG/Ca2+ signaling pathway in CCSMCs, that was related to the substituents at the key sites such as C8, C3, C4ʹ and C7 in the characteristic compounds.

Synthesis and Phytotoxic Evaluation of Isatin Derivatives Supported by 3D-QSAR Study.

Concerned about weed infestation, a major threat to food production and herbicide resistance that interferes in the mechanism of action of the main herbicides, we have synthesized eight isatin derivatives using the "Click Chemistry" approach through copper-catalyzed azide-alkyne cycloadditions (CuAAC). Sixteen isatin derivatives were evaluated for their phytotoxic activity against the seed culture of the model plants, Lactuca sativa and Allium cepa. Six of them showed phytotoxic activity similar to the positive control, trifluralin. Hypocotyl length measurement analysis in L. sativa revealed that triazole derivative 8 is more active than trifluralin. For A. cepa, root length measurement analyses revealed that 3, 10, 14, 16, and 17 were similar to the positive control trifluralin. Three-dimensional quantitative structure-activity relationship (3D-QSAR) comparative molecular field analysis (CoMFA) model construction using the acetolactate synthase (ALS) crystallographic structure displayed pki values of predicted inhibitory activity and contour maps revealing sterically bulky groups for 11, the CF3 group in ortho, and for 17, Br in ortho, favoring the inhibitory ALS activity.

Design, Synthesis, Analysis, Evaluation of Cytotoxicity Against MCF-7 Breast Cancer Cells, 3D QSAR Studies and EGFR, HER2 Inhibition Studies on Novel Biginelli 1,4-Dihydropyrimidines

1,4-Dihydropyrimidines are usually synthesized from Biginelli reaction which are well known for their anti-cancer activity. A series of novel Biginelli-1,4-dihydropyrimidines are rationally designed, synthesized, purified, analyzed by IR, NMR, Mass spectrometry and screened against MCF-7 breast cancer cells for their anti-cancer activity by measuring the cytotoxicity. Dihydropyrimidines exhibited weak to significant cytotoxicity proportionate to their anti-cancer activity. 14, 7 and 5 have exhibited potent cytotoxicity amongst the screened 33 dihydropyrimidines. Most potent compound 14 is further tested for inhibition of EGFR (epidermal growth factor receptor) and HER2 (human epidermal growth factor receptor 2) expression at 2 different concentrations by taking lapatinib as standard in flow cytometry. 42.02% and 36.45% of cells expressing EGFR and HER2 were inhibited at 500nM/L concentration. Furthermore, 3D-QSAR studies were executed to elucidate structure activity relationships in a 3D grid space by plotting experimental vs predicted cytotoxic activities.

3D-QSAR, drug-likeness, ADMET prediction, and molecular docking studies in silico of novel 5-oxo-1-thioxo-4,5-dihydro-1H-thiazolo[3,4-a]quinazoline derivatives as MALT1 protease inhibitors for the treatment of B cell lymphoma

3D-QSAR, drug-likeness, ADMET prediction, and molecular docking studies in silico of novel 5-oxo-1-thioxo-4,5-dihydro-1H-thiazolo[3,4-a]quinazoline derivatives as MALT1 protease inhibitors for the treatment of B cell lymphoma

Dual aromatase-steroid sulfatase inhibitors (DASI's) for the treatment of breast cancer: a structure guided ligand based designing approach

Dual aromatase-steroid sulfatase inhibitors (DASIs) lead to significant deprivation of estrogen levels as compared to a single target inhibition and thereby exhibited an additive or synergistic effect in the treatment of hormone-dependent breast cancer (HDBC). Triazole-bearing DASI’s having structural features of clinically available aromatase inhibitors are identified as lead structures for optimization as DASI’s. To identify the spatial fingerprints of target-specific triazole as DASI’s, we have performed molecular docking assisted Gaussian field-based comparative 3D-QSAR studies on a dataset with dual aromatase-STS inhibitory activities. Separate contours were generated for both aromatase and steroid sulphates showing respective pharmacophoric structural requirements for optimal activity. These developed 3D-QSAR models also showed good statistical measures with the excellent predictive ability with PLS-generated validation constraints. Comparative steric, electrostatic, hydrophobic, HBA, and HBD features were elucidated using respective contour maps for selective target-specific favourable activity. Furthermore, the molecular docking was used for elucidating the mode of binding as DASI’s along with the MD simulation of 100 ns revealed that all the protease-ligand docked complexes are overall stable as compared to reference ligand (inhibitor ASD or Irosustat) complex. Further, the MM-GBSA study revealed that compound 24 binds to aromatase as well as STS active site with relatively lower binding energy than reference complex, respectively. A comparative study of these developed multitargeted QSAR models along with molecular docking and dynamics study can be employed for the optimization of drug candidates as DASI’s. Communicated by Ramaswamy H. Sarma

Discovery of anti-colon cancer agents targeting wild-type and mutant p53 using computer-aided drug design

Mutations in the p53 gene are common and occur in over 50% of all cancers, as it is involved in DNA damage repair, cell cycle regulation and apoptosis. Moreover, the p53 gene is mutated in 70% of colon cancers. Therefore, the development of drugs to combat this mutation requires urgent attention. With this in mind, in silico drug design approaches were applied on quinoline derivatives with anticancer activity. In 3D-QSAR study, steric, electrostatic, hydrophobic and H-bond acceptor fields (SEHA) play an important role in prediction and design of new colon cancer compounds. Indeed, the two best CoMSIA/SEHA models with (Q 2 = 0.737, R 2 = 0.914, R pred 2 = 0.720) and (Q 2 = 0.738, R 2 = 0.919, R pred 2 = 0.739) show good prediction of human colon carcinoma HCT 116 (p53+/+) and (p53−/−) activities, respectively. Furthermore, the predictive ability and robustness of these models were tested by several validation methods. Molecular docking analyses reveal crucial interactions with the active sites of the p53 protein in both wild type and mutant. Based on these theoretical studies, we designed 10 new compounds with good anticancer activity potential, which were evaluated using ADMET properties. Molecular dynamics simulations were performed to confirm the detailed binding mode of the docking results. Finally, the MM-GBSA based on molecular dynamics simulation confirmed that the designed compounds were able to form stable hydrogen bonding interactions with the crucial residues, which are essential to overcome the p53 mutation in colon cancer. Communicated by Ramaswamy H. Sarma

A comparative quantitative structural assessment of benzothiazine-derived HDAC8 inhibitors by predictive ligand-based drug designing approaches

ABSTRACT Histone deacetylase 8 (HDAC8) is a verified biomolecular target associated with diverse diseases including cancer. Though several HDAC inhibitors emerged effective against such diseases, no selective HDAC8 inhibitor is approved to date. Therefore, the development of potent HDAC8-selective inhibitors is inevitable to combat such diseases. Here, some benzothiazine-derived HDAC8 inhibitors were considered for a comparative QSAR analysis which may elucidate the prime structural components responsible for modulating their efficacy. Several outcomes from these diverse modelling techniques justified one another and thus validated each other. The ligand-based pharmacophore modelling study identified ring aromatic, positive ionizable, and hydrophobic features as essential structural attributes for HDAC8 inhibition. Besides, MLR, HQSAR and field-based 3D-QSAR studies signified the utility of the positive ionizable and hydrophobic features for potent HDAC8 inhibition. Again, the field-based 3D-QSAR study provided useful insight regarding the substitution in the fused phenyl ring. Moreover, the current observations also validated the previously reported molecular docking observations. Based on the outcomes, some new molecules were designed and predicted. Therefore, this comparative structural analysis of these HDAC8 inhibitors will surely assist in the development of potent HDAC8 inhibitors as promising anticancer therapeutics in the future.

Combined computational approaches for developing new anti-Alzheimer drug candidates: 3D-QSAR, molecular docking and molecular dynamics studies of liquiritigenin derivatives

Butyrylcholinesterase is an acetylcholine-degrading enzyme involved in the memorization process, which is becoming an interesting target for the symptomatic treatment of Alzheimer's disease. In the present investigation, the structure–activity relationship of a set of Liquiritigenin derivatives recently revealed to be Butyrylcholinesterase inhibitors was studied basing on comparative field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMISA). As a result, performant models with high predictive capability have been developed (CoMFA model: R2 = 0.91, Q2 = 0.62, R2pred = 0.85; CoMISA model: R2 = 0.92, Q2 = 0.59, R2pred = 0.83) and implemented to design new Liquiritigenin derivatives with improved activity. Besides, the affinity of the designed derivatives towards the active site of Butyrylcholinesterase, was confirmed by molecular docking and molecular dynamics studies. Moreover, they exhibited good pharmacokinetics properties. Accordingly, the outcomes of the present investigations can provide important direction for the development of new anti-Alzheimer's drug candidates.

QSAR, molecular docking, ADMET properties in silico studies for a series of 7-propanamide benzoxaboroles as potent anti-cancer agents

The danger of ovarian cancer does not give any visible sign at the first stage of symptoms, for this reason, it is necessary to identify and discover effective drugs for this disease. In this work, we have performed 2D-QSAR and molecular docking studies for a series of 7-propanamide benzoxaboroles. The QSAR model was constructed using the seven descriptors, showed satisfactory internal and external validation parameters (R² train = 0.76, R² adjusted = 0.69, Q² cv = 0.62, R² test = 0.64) which passed the model acceptability criteria, the artificial neural network method showed a correlation coefficient of 0.88 with a 7-3-1. Molecular docking analysis was performed for the most active compound in the dataset, the resolved crystal structure of T. thermophilus LeuRS was obtained from the Protein Data Bank (PDB: 2V0G ), and the obtained docking results showed that the most important hydrogen interactions are ARG 719 and ASP 808, and two alkyl bonds (TYR 722, and ALA711), and a single Pi-anion bond GLU720 have a favorable effect on the biological activity. Finally, we made a study of ADMET properties on the ten selected most active compounds, the obtained results show that compounds number 1, 23, 26, 28, 32, and 37 have verified all the pharmacokinetic properties and toxicity, so we can select these different molecules as anti-cancer drug candidates.

Synthesis, Characterization and Evaluation of Some Novel 2-Mercaptobenzothiazole Derivatives: In Silico and Experimental Approach

Recently, QSAR technique and molecular docking have become widespread in designing new series of compounds, depending upon the different models developed, before actually synthesizing and testing them. Due to the diverse activity profile of substituted Benzothiazole, it has become a pharmacophore of interest. The main motive of the study was to design some novel 2- Mercaptobenzothiazole molecules with potential anti-inflammatory effect. Thus, in order to get a better insight into the structural features of 2- Mercaptobenzothiazole, a series of analogues were taken from the literature and 2D, 3D QSAR models were developed and molecular docking and ADME studies were also performed. For 2D QSAR study, stepwise forwarding variable selection method, coupled with Partial Least Square (SWF-PLS) regression-based method, was used to generate the best 2D model giving r2= 0.9425, q2=0.9018, F-value=90.0118, pred_r2=0.8976. In contrast, the forward stepwise variable selection k-nearest neighbour molecular field analysis approach was used to generate best 3D QSAR model (q2=0.8171 and pred_r2=0.7006). Docking studies were performed on 29 derivatives of 2-Mercaptobenzothiazoles. The ligands were prepared and docked against protein S. aureus TYrRS with a resolution of 3.2Å. The three derivatives K6, K18 and K20 were found to have the best docking scores (-48.44, -47.46, -48.52). Further, synthesis of these three derivatives was carried out. Spectral characterization was carried out by IR, 1H NMR and 13C NMR and all the structures were found to be in agreement with the data obtained. In vitro anti-inflammatory evaluation of these compounds was carried out by following the protein denaturation method and HRBC membrane stabilization method. Compound K20 displayed potential anti-inflammatory activity, which may be attributed to the electronegative group on the phenyl ring substituted on the pyrazole part of the pharmacophore.