Lycopene potentiates wound healing in streptozotocin-induced diabetic rats.

Background: Diabetes is a growing metabolic disease that is characterized by high blood sugar levels with life-threatening results. Diabetic wounds are a major problem because they do not resolve in few days. Major problems affecting wound healing are infection, age, stress, etc. at the wound site, and other associated disease conditions. Lycopene is a red pigment obtained from various fruits such as tomatoes, watermelon, and guava. It is a powerful antioxidant that scavenges reactive oxygen species and potential as nutraceuticals. It has reported antidiabetic, antioxidant, anti-obesity, anti-inflammatory, antihyperglycemic, and antiaging activities based on the literature. Objective: The objective of the current study is to find the wound-healing potential of lycopene emulgel (LE) and report the properties of the compound. Methods: Wound healing activity was assessed in Streptozotocin induced diabetic rats and control rats. Streptozotocin injection (55 mg/kg) was used to induce marked hyperglycaemia, compared with controls. The formulation was applied topically and was evaluated for efficacy. Results: Treatment of rats with lycopene emulgel (LE) topical application exhibited a significant reduction of wound closure of 95.3 and 88.9% and epithelisation within 21 days. Conclusion: The formulation was found to be novel, safe, and effective in the functional recovery of wounds.

Reconnoitering imidazopyridazines as anticancer agents based on virtual modelling approach: quantitative structure activity relationship, molecular docking and molecular dynamics.

Cancer is an unimpeded growth of cells leading to metathesis of cancer and eventually spread throughout the body. PIM kinases are the members of the serine threonine kinase playing role in cancer progression, differentiation and proliferation. Till date there is no single drug targeting PIM-1 kinase in the market, that has made itself a target in limelight for the discover of new anticancer agents. The contemporary research focusses on the development of new inhibitors of PIM-1 kinase by application of ligand-based and structure-based perspective of drug discovery namely 3D-QSAR, molecular docking and dynamics. The following study stated the correlation amid structural and biological activity of the compounds employing 3D-QSAR analysis. Three 3D-QSAR models were generated using 33 molecules from which the excellent model stated an encouraging conventional correlation coefficient (r2) 0.8651, cross validation coefficient (q2) 0.7609. Furthermore, the predicted correlation coefficient (r2 pred) 0.6274, respectively. Molecular docking studies revealed that the most active compound 26 resided in the active pocket of PIM-1 kinase establishing hydrogen bond interactions with Asp186 in the DFG motif; similarly, all other molecules were engaged within the active site of the PIM-1 kinase. Moreover, molecular dynamics simulation study stated the stability of the ligand in the active site of PIM-1 kinase protein by developing two hydrogen bonds throughout the trajectory of 100 ns. In nutshell, the output stated the successful application of ligand and structure-based strategy for the development of novel PIM-1 kinase inhibitors as anticancer agents.Communicated by Ramaswamy H. Sarma.

Machine learning facilitated structural activity relationship approach for the discovery of novel inhibitors targeting EGFR.

This research manuscript aims to find the most effective epidermal growth factor receptor (EGFR) inhibitors from millions of in house compounds through Machine Learning (ML) techniques. ML-based structure activity relationship (SAR) models were validated to predict biological activity of untested novel molecules. Six ML algorithms, including k nearest neighbour (KNN), decision tree (DT), Logistic Regression, support vector machine (SVM), multilinear regression (MLR), and random forest (RF), were used to build for activity prediction. Among these, RF classifier (accuracy for train and test set is 90% and 81%) and RF regressor (R2 and MSE for trainset is 0.83 and 0.29 and for test set, 0.69 and 0.46) showed good predictive performance. Also, the six most essential features that affect the biological activity parameter and highly contribute to model development were successfully selected by the variable importance technique. RF regression model was used to predict the biological activity expressed as pIC50 of nearly ten million molecules while RF classification model classifies those molecules into active, moderately active, and least active according to their predicted pIC50. Based on two models, thousand molecules from million molecules with higher predicted pIC50 values and classified as active were selected for molecular docking. Based on the docking scores, predicted pIC50, and binding interactions with MET769 residue, compounds, i.e., Zinc257233137, Zinc257232249, and Zinc101379788, were identified as potential EGFR inhibitors with predicted pIC50 7.72, 7.85, and 7.70. Dynamics studies were also performed on Zinc257233137 to illustrate that it has good binding free energy and stable hydrogen bonding interactions with EGFR. These molecules can be used for further research and proved to be the novel drugs for EGFR in cancer treatment.Communicated by Ramaswamy H. Sarma.

Benzimidazole-linked pyrazolo[1,5-a]pyrimidine conjugates: synthesis and detail evaluation as potential anticancer agents.

A library of benzimidazole briged pyrazolo[1,5-a]pyrimidine (6a-q) was designed, synthesized and subjected for evaluation for cytotoxic potential. Antiproliferative activity, ranging from 3.1-51.5 µM, was observed against a panel of cancer cell lines which included MCF-7 (breast cancer), A549 (lung cancer), HeLa (cervical cancer) and SiHa (cervical cancer). Among them, 6k, 6l, 6n and 6o have shown significant cytotoxicity and were investigated further to study their probable mechanism of action against MCF-7 cell line. Accumulation of cells at sub-G1 phase was observed in flow cytometric analysis. The detachment of cells from substratum and membrane blebbing seen under bright field microscopy supports the ability of these conjugates to induce apoptosis. Immunostaining and western blot analysis showed EGFR, p-EGFR, STAT3, and p-STAT3 significant downregulation. Western blot analysis demonstrated an elevated level of apoptotic proteins such as p53, p21, Bax, whereas a decrease in the antiapoptotic protein Bcl-2 and procaspase-9, confirming the ability of these conjugates to trigger cell death by apoptosis. EGFR kinase assay confirms the specific activity of conjugates. Molecular docking simulation study disclosed that these molecules fit well in ATP-binding pocket of EGFR. The analysis of docking poses and the atomic interactions of different conjugates rationalize the structural-activity relationship in this series. Benzimidazole-linked pyrazolo[1,5-a]pyrimidine conjugates were synthesized and evaluated for their anticancer potential. All the conjugates have significant anticancer potential. Further mechanistic studies revealed that these conjugates arrest cancer cell growth by EGFR/STAT3 inhibition.

Grafting of Natural Polymers and Gums for Drug Delivery Applications: A Perspective Review.

Natural polymers have received more attention because of their advantages over synthetic polymers such as abundant availability, low cost, biodegradability and non-toxicity. However, natural polymers suffer some limitations such as drop-in viscosity upon storage, uncontrolled hydration, solubility, inability to perform under high temperature and pressure (thermal stability), etc. In many instances above mentioned drawbacks of natural polymers limits their applications in drug delivery systems. Grafting of natural polymer leads to improved properties and characteristics of backbones of macromolecules such as improvement in gel strength, swelling index, mucoadhesion, drug targeting and drug release profile. Therefore, in recent decades grafting of the natural polymer has gained immense importance for the development of drug delivery systems. In addition to the pharmaceutical applications graft copolymers are extensively utilized in diversified fields. The present review is an attempt to define the grafting, various methods of polymer grafting and their application in drug delivery.

Computational modelling strategies in exploring triazolopyridazine PIM1 kinase inhibitors as anticancer agents.

BACKGROUND: PIM (Proviral Integration site for Moloney Murine Leukemia virus) kinases are members of the class of kinase family serine/ threonine kinases, which play a crucial role in cancer development. As there is no drug in the market against PIM-1, kinase has transpired as a budding and captivating target for discovering new anticancer agents targeting PIM-1 kinase. AIM: The current research pondered the development of new PIM-1 kinase inhibitors by applying a ligand-based and structure-based drug discovery approach involving 3D QSAR, molecular docking, and dynamics simulation. METHOD: In this study, association allying the structural properties and biological activity was undertaken using 3D-QSAR analysis. The 3D-QSAR model was generated with the help of 35 compounds from which the best model manifested an appreciated cross-validation coefficient (q2) of 0.8866 and conventional correlation coefficient (r2) of 0.9298, respectively and predicted correlation coefficient (r2 pred) was obtained as 0.7878. RESULT: The molecular docking analysis demonstrated that the analogs under analysis occupied the active site of PIM-1 kinase receptor and interactions with Lys67 in the catalytic region, Asp186 in the DFG motif, and Glu171 were noticed with numerous compounds. DISCUSSION: Furthermore, the molecular dynamics simulation study stated that the ligand portrayed the strong conformational stability within the active site of PIM-1 kinase protein, forming of two hydrogen bonds until 100 ns, respectively. CONCLUSION: Overall outcomes of the study revealed that applications of the ligand-based drug discovery approach and structure-based drug discovery strategy conceivably applied to discovering new PIM-1 kinase inhibitors as anticancer agents.

Topical advances in PIM kinases and their inhibitors: Medicinal chemistry perspectives.

Cytosolic PIM kinases are the members of serine/ threonine family play a crucial role in the cancer progression and development. Overexpression of PIM kinases is observed in various types of cancers including prostate, hematological, pancreatic, breast carcinoma and likewise. PIM kinases have now been considered as limelight target for the discovery of new molecules as novel anticancer agents as no drug is in the market targeting PIM kinases. In the last two decades, numerous PIM kinase inhibitors have been developed and few of them were in clinical trial phases but could not pass the pipeline of the clinical trials. The present comprehensive review intends to cover biological and the structural aspects of PIM kinases and also medicinal chemistry of PIM inhibitors developed in recent years.

Design, Synthesis and Biological Evaluation of New Cycloalkyl Fused Quinolines Tethered to Isatin Schiff Bases as Cholinesterase Inhibitors.

AIMS AND OBJECTIVE: Alzheimer's disease is now a most prevalent neurodegenerative disease of central nervous system leading to dementia in elderly population. Numerous pathological changes have been associated in the progression of Alzheimer's disease. One of such pathological hypotheses is declined cholinergic activity which eventually leads to cognitive and memory deficits. Inhibition o f cholinesterases will apparently elevate acetyl choline levels which is benefactor on cognitive symptoms of the disease. This manuscript describes the new tacrine derivatives tethered to isatin Schiff bases through alkanoyl linker and screened for cholinesterase inhibitory activity. MATERIALS AND METHODS: Tacrine and two more cycloalkyl ring fused quinolones were synthesized and converted to N-cycloalkyl fused quinoline chloroamides. Isatin Schiff bases were also synthesized by the reaction between isatin and substituted aromatic anilines and in subsequent reaction, isatin Schiff bases were reacted with cycloalkyl fused quinolones to afford anticipated compounds 10a-i, 11a-i and 12a-i. All the compounds have been screened for acetyl- and butyrylcholinesterase inhibitory activity and in vivo behavioral studies. Binding interactions of the desired compounds have also been studied by docking them in active site of both cholinesterases. RESULTS: Three compounds 12d, 12e and 12h with propionyl and butyroyl linker between amine and isatin Schiff base scaffold have shown potent acetyl- and butyrylcholinesterase inhibitory activity. However most potent cholinesterase inhibitor was 13d with IC50 value of 0.71±0.004 and 1.08±0.02 µM against acetyl- and butyrylcholinesterases respectively. The hepatotoxicity of potent compounds revealed that the tested compounds were less hepatotoxic than tacrine and also exhibited encouraging in vivo behavioral studies in test animals. Docking studies of all the molecules disclosed close hydrogen bond interactions within the binding site of both cholinesterases. CONCLUSION: New cycloalkyl fused quinolones tethered with alkanoyl linker to isatin Schiff bases endowed significant and potent cholinesterase inhibitory activities. Few of the compounds have also exhibited lesser hepatotoxicity and all the synthesized compounds were good in behavioral studies. Molecular docking studies also indicated close interactions in active site of cholinesterases.

Novel Aminopyrazole Tagged Hydrazones as Anti-Tubercular Agents: Synthesis and Molecular Docking Studies.

BACKGROUND: Pyrazole derivatives have been reported to possess numerous pharmacological activities viz., anti-inflammatory, antipsychotic, etc. Our group has disclosed that pyrazole benzamides display potent antibacterial and anti-tubercular activities. OBJECTIVE: Synthesis of new pyrazole acetamides which possess hydrazone group to be evaluated for antitubercular activity. METHODS: The key intermediate 5-aminopyrazole was synthesized with the known procedure, which is then converted into chloroacetamide. This compound than resulted in hydrazine derivative and finally converted into aromatic hydrazones. All the compounds were screened for antitubercular activity. RESULTS: All the synthesized compounds have been characterized by their spectral data obtained and subjected to anti-tubercular activity. Among all the twenty tested compounds, three compounds, 5a5, 5b5 and 5b7 have demonstrated MIC value of 3.12 µg/mL against MTB H37Rv. Docking studies revealed important hydrogen bonding interactions with InhA. CONCLUSION: Three compounds 5a5, 5b5 and 5b7 were found to be most potent among the series of compounds. Docking studies of compounds explained the presence of hydrogen bonding and π- π stacking interactions with InhA. Further synthesis of more such derivatives with optimized groups would produce compounds with more potent anti-tubercular activity.

Synthesis, Characterization, Antitubercular and Anti-Inflammatory Activity of New Pyrazolo[3,4-d]Pyrimidines.

AIMS AND OBJECTIVE: Copious proinflammatory cytokines including TNF-α and IL-1ß are involved in progression of inflammation in human body. Inhibition of signaling mediated by proinflammatory cytokines offer effective in the treatment of inflammatory diseases. The treatment of dreadful infectious disease mycobacterium tuberculosis still remains a challenge owing to resistance to multiple drugs hence an urgent need for newer drugs. Pyrazolo[3,4-d]pyrimidines have been disclosed to possess numerous pharmacological activities including anti-inflammatory, antimicrobial and antitubercular activities. Here in we report the synthesis of pyrazolo[3,4-d]pyrimidines for anti-inflammatory and antitubercular activities. MATERIALS AND METHODS: The targeted compounds having pyrazolo[3,4-d]pyrimidine scaffold 8a-m were synthesized in three step reactions with the formation of key intermediate 5-amino-4-- cyno-1-phenyl pyrazole which upon cyclization resulted in 4-amino pyrazolo[3,4-d]pyrimidine for subsequent benzoylation with substituted benzoyl chlorides to form 8a-m. Antiinflammatory activity of 8a-m was assessed at 25 mg/Kg dose and minimum inhibitory concentration against gram positive, gram negative and mycobacteria was also performed. Binding interactions were also measured in binding pocket of p38 kinase. RESULTS: Four compounds 8a, 8b, 8e and 8i significant anti-inflammatory activity in rat paw edema model induced by carrageenan and among all 8b was potent with 80.6% activity. Numerous compounds exhibited potent activity against fungal strains than bacterial strains, compound 8k was most potent against gram negative bacteria Klebsiella pneumoniae. Compounds 8d, 8e and 8f exhibited antitubercular activity with MIC value of 6.25 µg/mL. CONCLUSION: Substituted N-benzoylated amino pyrazolo[3,4-d]pyrimidines endowed significant and potent anti-inflammatory and antimicrobial activities. Molecular docking studies also revealed favorable interactions in active site of p38 kinase.

A comparative evaluation of the antibacterial efficacy of Thymus vulgaris, Salvadora persica, Acacia nilotica, Calendula arvensis, and 5% sodium hypochlorite against Enterococcus faecalis: An in-vitro study.

OBJECTIVES: The aim of this study is to evaluate and compare the antibacterial efficacy of Thymus vulgaris, Salvadora persica, Acacia nilotica, Calendula arvensis, and 5% sodium hypochlorite against Enterococcus faecalis. METHODOLOGY: Herbal extracts of T. vulgaris, S. persica, A. nilotica and C. arvensis were prepared. Tryptone soya broth was used to grow E. faecalis and agar plates were prepared. The tested solutions (Group A: 5% NaOCl, Group B: 20% T. vulgaris, Group C: 12.5% S. persica, Group D: 10% A. nilotica, Group E: 10% C. arvensis) were added to the wells made on agar media. Agar diffusion test was performed. Plates were incubated at 37°C for 24 h. Bacterial zones of inhibition were recorded. RESULTS: The data were analyzed statistically by Analysis of Variance (ANOVA) and post hoc comparison by Tukey's t-test. The highest zone of inhibition against E. faecalis was shown by 5% NaOCl, followed by 10% C. arvensis, 20% T. vulgaris and 10% A. nilotica showed similar comparable antibacterial activity. The least zone of inhibition was showed by S. persica. CONCLUSION: 5% NaOCl showed the maximum antibacterial activity, and herbal products demonstrated significant antibacterial activity against E. faecalis and can be employed as an alternative to NaOCl.

Simultaneous Rupture of the Bladder and Pelvicaliceal System Because of Blunt Abdominal Trauma: A Rare Case.

We present a unique case of simultaneous rupture of the bladder and left renal pelvis after blunt trauma to the lower abdomen. To the best of our knowledge, this has not yet been reported in the literature. Another unusual aspect of this case was that the bladder rupture was bilateral, with both an extra- and intraperitoneal component. The management of this case was challenging. This involved an emergency laparotomy to repair the bladder tear, followed by a nephrostomy. This was followed by left ureteral stent insertion using a rendezvous technique. The case also highlights the role of expectant conservative management relating to the concurrent left renal pelvic rupture.

Substituted Benzamides from Anti-inflammatory and p38 Kinase Inhibitors to Antitubercular Activity: Design, Synthesis and Screening.

BACKGROUND: Twenty one amide compounds possessing phenoxy/benzyloxy/pyridinyl groups have been synthesized by benzoylation of respective amines in presence of base with moderate to encouraging yields. Upon confirmation of structure, compounds were subjected for p38 kinase inhibitory, anti-inflammatory, antimicrobial and antitubercular activities. METHOD: Anti-inflammatory activity was determined using carrageenan induced rat paw edema model while p38 kinase inhibitory activity was studied using ELISA method and serial dilution method was employed to determine MICs. Two compounds 4g and 4n showed over 30% p38 kinase inhibitory activity at 10 µM and best anti-inflammatory activity was found for compounds 4g, 4i, 4n and 4o which exhibited to reduce paw edema over 70%. Compound 4b was observed to be the most potent against gram +ve organisms with MIC value of 1.6 µG/mL and compound 4u displayed potent antibacterial activity against gram negative organisms. CONCLUSION: Most encouraging antitubercular activity was noticed for compounds 4u, 4r and 4k with 6.25, 12.5 and 12.5 µG/mL Further, in order to know the binding site interactions, a docking simulations of compounds was performed. These preliminary results will certainly show fruitful directions to improve the activities of compounds.

High prevalence of cardiometabolic risk factors in young employees of Information Technology industry.

BACKGROUND: We assessed the burden of cardiometabolic risk factors in Information Technology (IT) employees as they are exposed to adverse lifestyle. MATERIALS AND METHODS: In this cross-sectional study, health records were obtained from two IT industries in Pune. Prevalence of cardiometabolic risk factors [hyperglycemia, high blood pressure (BP), hypertriglyceridemia, high low-density lipoprotein (LDL)-cholesterol, low high-density lipoprotein (HDL)-cholesterol, and overweight/obesity] was determined using standard cutoffs. We also examined clustering of risk factors (≥two risk factors). RESULTS: Data were available on 1,350 of 5,800 employees (mean age: 33 ± 6 years, 78% men). Prevalence of diabetes and hypertension was 2.5% and 13.5%, respectively. Prevalence of prediabetes, borderline high BP, hypertriglyceridemia, high LDL-cholesterol, low HDL-cholesterol, and overweight/obesity was 6.5%, 20.3%, 21%, 22.1%, 70.1%, and 51.4%, respectively. Risk factor clustering was observed in 63.5% that increased with age (P < 0.001). CONCLUSION: Given the high burden of risk factors at relatively young age, spreading awareness and promoting healthy lifestyle through workplace interventions are warranted.

Pyrazole derivatives as potent inhibitors of c-Jun N-terminal kinase: synthesis and SAR studies.

Mitogen activated protein kinases including c-Jun N-terminal kinase play an indispensable role in inflammatory diseases. Investigation of reported JNK-1 inhibitors indicated that diverse heterocyclic compounds bearing an amide group rendered potent JNK-1 inhibitory activity which prompted us to synthesize new JNK-1 inhibitors containing a pyrazole heterocyclic group. A DABCO mediated 1,3-dipolar cycloaddition reaction in neat resulted in pyrazole carboxylic acid which was converted to desired amides. Upon confirmation of the structures, all the compounds were screened for JNK-1 inhibitory activity and in vivo anti-inflammatory activity. Several synthesized analogues have exhibited JNK-1 inhibitory activity less than 10 µM, in particular compounds 9 c, 10 a and 10 d were found to be potent among all the compounds.

Synthesis, characterization and anti-inflammatory activity of N-(4- phenyl-1, 3-thiazol-2-yl)-N'-phenylureas.

A series of N-(4-phenyl-1, 3-thiazol-2-yl)-N'- phenylureas (5a-z) was synthesized from 2-amino-4-substituted phenylthiazoles and phenylisocyanates. The newly synthesized compounds were characterized by IR, (1)H NMR and Mass spectral data. All the twenty six N-(4-phenyl-1, 3-thiazol-2-yl)-N'-phenylurea derivatives were screened for antiinflammatory activity by following carrageenan induced rat paw edema method. Among the compounds screened, N-[4- (4-methoxy phenyl)-1, 3-thiazol-2-yl)-N'-phenylurea and N-[4-(4-methoxy phenyl-1, 3-thiazol-2-yl)-N'-(4-bromophenyl) urea were found to be more potent. The molecular docking interaction of aforementioned urea compounds revealed the traditional type II p38 kinase inhibitor's interactions in the DFG out active site.

Synthesis, antibacterial, antifungal and antitubercular activities of N-pyrazolylbenzamide derivatives.

A series of new N-pyrazolylbenzamides (5a-x) were synthesized by aroylation of 5-amino-1-phenyl-3-tbutylpyrazole. The structures of synthesized compounds were established based on spectral (FTIR, (1)H NMR, ESI Mass) analysis and purity was ascertained by HPLC. The antibacterial screening revealed that seven molecules exhibited an excellent antibacterial activity and eight compounds demonstrated considerable antifungal activity. Three molecules of the series 5e, 5s and 5w were found to be highly effective against Klebsilla pneumoneia with MIC of 3.12 µg/ml. Compounds 5b, 5f, 5g and 5o exhibited significant antitubercular activity with MIC of 12.5 µg/ml.

Synthesis, p38 kinase inhibitory and anti-inflammatory activity of new substituted benzimidazole derivatives.

P38 mitogen activated protein kinases have been found to involve in the production and release of unwarranted levels of pro-inflammatory cytokines including TNFα and IL-1ß in numerous inflammatory diseases. A new series of molecules, 5-substituted benzoylamino-2-substituted phenylbezimidazoles has been synthesized from 4-nitro-1, 2- diaminobenzene. The synthesized compounds were characterized by FTIR, 1HNMR and Mass. The final compounds were screened for in vitro p38 kinase inhibitory and in vivo anti-inflammatory activity. Three compounds from the series demonstrated nearly 50% inhibition of p38 kinase in the in vitro screening method at 10 µM concentration and two molecules exhibited greater than 75% inhibition of paw oedema volume during the first hour. The docking study of synthesized molecule revealed a new binding pose in ATP binding pocket.

Design, synthesis and characterization of N', N"-diaryl ureas as p38 kinase inhibitors.

Kinases have been known as important molecular targets for various diseases and p38 kinase is found to be vital target among all mitogen activated protein kinases for inflammatory diseases. P38 kinase inhibitors bearing urea scaffold have shown potent kinase inhibitory activity and also selectivity over other kinases. We present here the synthesis, p38 kinase inhibitory and anti-inflammatory activities of compounds containing N', N"-diarylurea scaffold. Compound 7f demonstrated IC50 value of 1.09 µM in p38 kinase assay and 79.41% inhibition of rat paw edema at the 2nd hour of carrageenan challenge. The molecular docking studies of synthesized compounds indicated some of the important hydrogen bonding interactions and also revealed the minor change in the binding pose when compared to BIRB796.

Strategies to design pyrazolyl urea derivatives for p38 kinase inhibition: a molecular modeling study.

The p38 protein kinase is a serine-threonine mitogen activated protein kinase, which plays an important role in inflammation and arthritis. A combined study of 3D-QSAR and molecular docking has been undertaken to explore the structural insights of pyrazolyl urea p38 kinase inhibitors. The 3D-QSAR studies involved comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA). The best CoMFA model was derived from the atom fit alignment with a cross-validated r (2 )(q (2)) value of 0.516 and conventional r (2) of 0.950, while the best CoMSIA model yielded a q (2) of 0.455 and r (2) of 0.979 (39 molecules in training set, 9 molecules in test set). The CoMFA and CoMSIA contour maps generated from these models provided inklings about the influence of interactive molecular fields in the space on the activity. GOLD, Sybyl (FlexX) and AutoDock docking protocols were exercised to explore the protein-inhibitor interactions. The integration of 3D-QSAR and molecular docking has proffered essential structural features of pyrazolyl urea inhibitors and also strategies to design new potent analogues with enhanced activity.