Browsing by Author "Sushant Kumar Shrivastava"

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Deciphering oral cancer subtypes: Integrating differential gene expression and pathway analysis followed by non-negative matrix factorization transcription analysis
(Elsevier Ltd, 2025) Anoop Kumar Tiwari; Devansh Jain; Jayesh Kumar Tiwari; Shyam Kishore; Akhilesh Kumar Singh; Sushant Kumar Shrivastava; Arun Khattri
Oral cancer is a major public health concern around the globe, and its classification relies on factors such as habitual status and tumor stages. However, a significant gap exists in understanding oral cancer patients' molecular and genomic characteristics. This study aims to bridge this gap by analyzing International Cancer Genome Consortium (ICGC's) oral cancer data, which identified 2270 differentially expressed genes related to oral cancer. We employed pathway enrichment analysis, highlighting key pathways including hypoxia, VEGF, PI3K, and TGF-β, and STAT2, E2F4, and SP1 transcription factors enriched in tumor samples compared to normal samples. Moreover, we utilized a non-negative matrix factorization (NMF) technique for unsupervised subtype discovery and identified three distinct tumor subgroups. Each subgroup exhibited unique molecular profiles, with pathways related to TNF-α, NF-κB, and hypoxia enriched across all groups. Notably, transcription factor analysis revealed crucial differences: subgroup A was enriched in EGR1, TP53, and HIF1A; subgroup B showed high levels of CDX2 and HNF4A; while subgroup C was characterized by enrichment in ATF4 and E2F4. These findings suggest the feasibility of classifying oral squamous cell carcinoma (OSCC) patients based on gene expression profiles, laying a foundational framework for future research aimed at personalized treatment strategies. © 2025 The Authors
Design and development of benzyl piperazine linked 5-phenyl-1,2,4-triazole-3-thione conjugates as potential agents to combat Alzheimer's disease
(Academic Press Inc., 2023) Pidugu Venkata Ravi Kiran; Digambar Kumar Waiker; Akash Verma; Poorvi Saraf; Bhagwati Bhardwaj; Hansal Kumar; Abhinav Singh; Pradeep Kumar; Namrata Singh; Saripella Srikrishna; Surendra Kumar Trigun; Sushant Kumar Shrivastava
Our present work demonstrates the molecular hybridization-assisted design, synthesis, and biological evaluation of 22 benzylpiperazine-linked 1,2,4-triazole compounds (PD1-22) as AD modifying agents. All the compounds were tested for their in vitro hChEs, hBACE-1, and Aβ-aggregation inhibition properties. Among them, compound PD-08 and PD-22 demonstrated good hChE and hBACE-1 inhibition as compared to standards donepezil and rivastigmine. Both compounds displaced PI from PAS at 50 µM concentration which was comparable to donepezil and also demonstrated anti-Aβ aggregation properties in self- and AChE-induced thioflavin T assay. Both compounds have shown excellent BBB permeation via PAMPA-BBB assay and were found to be non-neurotoxic at 80 µM concentration against differentiated SH-SY5Y cell lines. Compound PD-22 demonstrated an increase in rescued eye phenotype in Aβ-phenotypic drosophila AD model and amelioration of behavioral deficits in the Aβ-induced rat model of AD. The in-silico docking studies of compound PD-22 revealed a good binding profile towards CAS and PAS residues of AChE and the catalytic dyad of the BACE-1. The 100 ns molecular dynamics simulation studies of compound PD-22 complexed with AChE and BACE-1 enzymes suggested stable ligand-protein complex throughout the simulation run. Based on our findings compound PD-22 could further be utilized as a lead to design a promising candidate for AD therapy © 2023 Elsevier Inc.
Design, Synthesis, and Biological Evaluation of Piperazine and N-Benzylpiperidine Hybrids of 5-Phenyl-1,3,4-oxadiazol-2-thiol as Potential Multitargeted Ligands for Alzheimer’s Disease Therapy
(American Chemical Society, 2023) Digambar Kumar Waiker; Akash Verma; None Akhilesh; T.A. Gajendra; Namrata Singh; Anima Roy; Hagera Dilnashin; Vinod Tiwari; Surendra Kumar Trigun; Surya P. Singh; Sairam Krishnamurthy; Prem Lama; Vincent Jo Davisson; Sushant Kumar Shrivastava
Our present work demonstrates the successful design and synthesis of a new class of compounds based upon a multitargeted directed ligand design approach to discover new agents for use in Alzheimer’s disease (AD). All the compounds were tested for their in vitro inhibitory potential against human acetylcholinesterase (hAChE), human butylcholinesterase (hBChE), β-secretase-1 (hBACE-1), and amyloid β (Aβ) aggregation. Compounds 5d and 5f have shown hAChE and hBACE-1 inhibition comparable to donepezil, while hBChE inhibition was comparable to rivastigmine. Compounds 5d and 5f also demonstrated a significant reduction in the formation of Aβ aggregates through the thioflavin T assay and confocal, atomic force, and scanning electron microscopy studies and significantly displaced the total propidium iodide, that is, 54 and 51% at 50 μM concentrations, respectively. Compounds 5d and 5f were devoid of neurotoxic liabilities against RA/BDNF (RA = retinoic acid; BDNF = brain-derived neurotrophic factor)-differentiated SH-SY5Y neuroblastoma cell lines at 10-80 μM concentrations. In both the scopolamine- and Aβ-induced mouse models for AD, compounds 5d and 5f demonstrated significant restoration of learning and memory behaviors. A series of ex vivo studies of hippocampal and cortex brain homogenates showed that 5d and 5f elicit decreases in AChE, malondialdehyde, and nitric oxide levels, an increase in glutathione level, and reduced levels of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) mRNA. The histopathological examination of mice revealed normal neuronal appearance in the hippocampal and cortex regions of the brain. Western blot analysis of the same tissue indicated a reduction in Aβ, amyloid precursor protein (APP)/Aβ, BACE-1, and tau protein levels, which were non-significant compared to the sham group. The immunohistochemical analysis also showed significantly lower expression of BACE-1 and Aβ levels, which was comparable to donepezil-treated group. Compounds 5d and 5f represent new lead candidates for developing AD therapeutics. © 2023 American Chemical Society.
Design, synthesis, and biological evaluation of some 2-(3-oxo-5,6-diphenyl-1,2,4-triazin-2(3H)-yl)-N-phenylacetamide hybrids as MTDLs for Alzheimer's disease therapy
(Elsevier Masson s.r.l., 2024) Digambar Kumar Waiker; Akash Verma; T.A. Gajendra; Namrata; Anima Roy; Pradeep Kumar; Surendra Kumar Trigun; Saripella Srikrishna; Sairam Krishnamurthy; Vincent Jo Davisson; Sushant Kumar Shrivastava
Inspite of established symptomatic relief drug targets, a multi targeting approach is highly in demand to cure Alzheimer's disease (AD). Simultaneous inhibition of cholinesterase (ChE), β secretase-1 (BACE-1) and Dyrk1A could be promising in complete cure of AD. A series of 18 diaryl triazine based molecular hybrids were successfully designed, synthesized, and tested for their hChE, hBACE-1, Dyrk1A and Aβ aggregation inhibitory potentials. Compounds S-11 and S-12 were the representative molecules amongst the series with multi-targeted inhibitory effects. Compound S-12 showed hAChE inhibition (IC50 value = 0.486 ± 0.047 μM), BACE-1 inhibition (IC50 value = 0.542 ± 0.099 μM) along with good anti-Aβ aggregation effects in thioflavin-T assay. Only compound S-02 of the series has shown Dyrk1A inhibition (IC50 value = 2.000 ± 0.360 μM). Compound S-12 has also demonstrated no neurotoxic liabilities against SH-SY5Y as compared to donepezil. The in vivo behavioral studies of the compound S-12 in the scopolamine- and Aβ-induced animal models also demonstrated attanuation of learning and memory functions in rats models having AD-like characteristics. The ex vivo studies, on the rat hippocampal brain demonstrated reduction in certain biochemical markers of the AD brain with a significant increase in ACh level. The Western blot and Immunohistochemistry further revealed lower tau, APP and BACE-1 molecular levels. The drosophilla AD model also revealed improved eyephenotype after treatment with compound S-12. The molecular docking studies of the compounds suggested that compound S-12 was interacting with the ChE-PAS & CAS residues and catalytic dyad residues of the BACE-1 enzymes. The 100 ns molecular dynamics simulation studies of the ligand-protein complexed with hAChE and hBACE-1 also suggested stable ligand–protein confirmation throughout the simulation run. © 2024 Elsevier Masson SAS
Design, Synthesis, and Biological Investigation of Quinazoline Derivatives as Multitargeting Therapeutics in Alzheimer’s Disease Therapy
(American Chemical Society, 2024) Akash Verma; Digambar Kumar Waiker; Neha Singh; Anima Roy; Namrata Singh; Poorvi Saraf; Bhagwati Bhardwaj; Sairam Krishnamurthy; Surendra Kumar Trigun; Sushant Kumar Shrivastava
An efficient and promising method of treating complex neurodegenerative diseases like Alzheimer’s disease (AD) is the multitarget-directed approach. Here in this work, a series of quinazoline derivatives (AV-1 to AV-21) were rationally designed, synthesized, and biologically evaluated as multitargeted directed ligands against human cholinesterase (hChE) and human β-secretase (hBACE-1) that exhibit moderate to good inhibitory effects. Compounds AV-1, AV-2, and AV-3 from the series demonstrated balanced and significant inhibition against these targets. These compounds also displayed excellent blood−brain barrier permeability via the PAMPA-BBB assay. Compound AV-2 significantly displaced propidium iodide (PI) from the acetylcholinesterase-peripheral anionic site (AChE-PAS) and was found to be non-neurotoxic at the maximum tested concentration (80 μM) against differentiated SH-SY5Y cell lines. Compound AV-2 also prevented AChE- and self-induced Aβ aggregation in the thioflavin T assay. Additionally, compound AV-2 significantly ameliorated scopolamine and Aβ-induced cognitive impairments in the in vivo behavioral Y-maze and Morris water maze studies, respectively. The ex vivo and biochemical analysis further revealed good hippocampal AChE inhibition and the antioxidant potential of the compound AV-2. Western blot and immunohistochemical (IHC) analysis of hippocampal brain revealed reduced Aβ, BACE-1, APP/Aβ, and Tau molecular protein expressions levels. The pharmacokinetic analysis of compound AV-2 demonstrated significant oral absorption with good bioavailability. The in silico molecular modeling studies of lead compound AV-2 moreover demonstrated a reasonable binding profile with AChE and BACE-1 enzymes and stable ligand−protein complexes throughout the 100 ns run. Compound AV-2 can be regarded as the lead candidate and could be explored more for AD therapy. © 2024 American Chemical Society.
Design, synthesis, and evaluation of benzhydrylpiperazine-based novel dual COX-2/5LOX inhibitors with anti-inflammatory and anticancer activity
(Royal Society of Chemistry, 2024) Poorvi Saraf; Bhagwati Bhardwaj; Akash Verma; Mohammad Aquib Siddiqui; Himanshu Verma; Pradeep Kumar; Samridhi Srivastava; Sairam Krishnamurthy; Saripella Srikrishna; Sushant Kumar Shrivastava
Piperazine derivatives were screened using the ChEMBL database, paving the way for the design, synthesis, and evaluation of a novel series of dual COX-2/5-LOX inhibitors and identifying their role in mitigating cancer cell proliferation. Compound 9d with 4-Cl substitution at the terminal phenyl ring showed promising inhibition of COX-2 (IC50 = 0.25 ± 0.03 μM) and 5-LOX (IC50 = 7.87 ± 0.33 μM), outperforming the standards celecoxib (IC50 = 0.36 ± 0.023 μM) and zileuton (IC50 = 14.29 ± 0.173 μM), respectively. The two most active derivatives 9d and 9g indicated a significant anti-inflammatory response in a paw edema model by inhibiting PGE2, IL-6, and TNF-α and an increase in IL-10 concentrations. Interestingly, 9d effectively reduced pain by 55.78%, closely comparable to the 59.09% exhibited by the standard indomethacin, and was also devoid of GI, liver, kidney, and cardiac toxicity. Furthermore, 9d demonstrated anti-cancer potential against in vitro A549, COLO-205, and MIA-PA-CA-2 human cancer cell lines and an in vivo Drosophila cancer model. The pharmacokinetic investigations revealed that 9d has good oral absorption characteristics. © The Royal Society of Chemistry 2025.
Development and Evaluation of Some Molecular Hybrids of N-(1-Benzylpiperidin-4-yl)-2-((5-phenyl-1,3,4-oxadiazol-2-yl)thio) as Multifunctional Agents to Combat Alzheimer’s Disease
(American Chemical Society, 2023) Digambar Kumar Waiker; Akash Verma; Poorvi Saraf; T.A. Gajendra; Sairam Krishnamurthy; Rameshwar Nath Chaurasia; Sushant Kumar Shrivastava
A series of some novel compounds (SD-1-17) were designed following a molecular hybridization approach, synthesized, and biologically tested for hAChE, hBChE, hBACE-1, and Aβ aggregation inhibition potential to improve cognition and memory functions associated with Alzheimer’s disease. Compounds SD-4 and SD-6 have shown multifunctional inhibitory profiles against hAChE, hBChE, and hBACE-1 enzymes in vitro. Compounds SD-4 and SD-6 have also shown anti-Aβ aggregation potential in self- and acetylcholinesterase (AChE)-induced thioflavin T assay. Both compounds have shown a significant propidium iodide (PI) displacement from the cholinesterase-peripheral active site (ChE-PAS) region with excellent blood-brain barrier (BBB) permeability and devoid of neurotoxic liabilities. Compound SD-6 ameliorates cognition and memory functions in scopolamine- and Aβ-induced behavioral rat models of Alzheimer’s disease (AD). Ex vivo biochemical estimation revealed a significant decrease in malonaldehyde (MDA) and AChE levels, while a substantial increase of superoxide dismutase (SOD), catalase, glutathione (GSH), and ACh levels is seen in the hippocampal brain homogenates. The histopathological examination of brain slices also revealed no sign of neuronal or any tissue damage in the SD-6-treated experimental animals. The in silico molecular docking results of compounds SD-4 and SD-6 showed their binding with hChE-catalytic anionic site (CAS), PAS, and the catalytic dyad residues of the hBACE-1 enzymes. A 100 ns molecular dynamic simulation study of both compounds with ChE and hBACE-1 enzymes also confirmed the ligand-protein complex’s stability, while quikprop analysis suggested drug-like properties of the compounds. © 2023 The Authors. Published by American Chemical Society.
Discovery of platelet glycoprotein VI receptor antagonists and their neuroprotective activity: an in silico, in vitro, and in vivo study
(Springer Science and Business Media Deutschland GmbH, 2025) Mohammad Aquib Siddiqui; Poorvi Saraf; Sushant Kumar Shrivastava; Sudha Madhavi Penumaka; Debabrata Mandal; Ravi Saini; Abhishek Pathak; Ramakrishna Kakarla; Sairam Krishnamurthy
The present study utilized a drug repurposing approach to identify potential GPVI receptor antagonists among FDA-approved drugs. Computational and molecular dynamics simulations revealed that adapalene and ranolazine exhibit strong binding affinities to GPVI receptors and stabilize GPVI proteins, respectively. Both compounds inhibited collagen-induced platelet aggregation, evidenced by the suppression of Syk tyrosine kinase expression, a marker of platelet activation, via GPVI stimulation, as confirmed through flow cytometry analysis. Further analysis using circular dichroism and Raman spectroscopy indicated that collagen exposure induced conformational changes in the α-helical domains of platelets, which were stabilized upon treatment with adapalene and ranolazine. Moreover, thrombotic events can lead to cerebral cell death due to hypoxia, which may be mitigated by neuroprotective compounds. Adapalene and ranolazine were assessed for their neuroprotective capabilities. The results showed that these compounds exhibited neuroprotective effects in SHSY5Y neuroblastoma cells subjected to oxygen–glucose deprivation/reperfusion (OGD/R) injury, reducing HIF-1α expression, ROS production, lipid peroxidation, and caspase-3 levels, while also improving mitochondrial membrane potential and glutathione levels. Acridine orange and propidium iodide staining studies further confirmed a decrease in apoptosis. In the FeCl3-induced carotid artery thrombosis model, ranolazine effectively inhibited platelet aggregation by modulating GPVI receptor activity, reducing intracellular calcium levels, and enhancing cAMP signaling. It also suppressed critical platelet activation mediators, including COX-1, TXB2, and PGE2, thereby mitigating thrombus formation. Collectively, these results suggest that adapalene and ranolazine may serve as multimodal therapeutic agents with the potential to treat both thrombotic and neurological diseases. Future studies focusing on the adapalene and ranolazine molecular mechanisms, bleeding risk, dose titration, and long-term safety while managing thrombotic disorders have to be investigated. © King Abdulaziz City for Science and Technology 2025.
In silico and in vitro evaluation of extract derived from Dunaliella salina, a halotolerant microalga for its antifungal and antibacterial activity
(Taylor and Francis Ltd., 2023) Urmilesh Singh; Laxmi; Prabhakar Singh; Ankit Kumar Singh; Sweksha Singh; Deepak Kumar; Sushant Kumar Shrivastava; Ravi Kumar Asthana
In the present study little explored halotolerant wall-less green alga Dunaliella salina was found to be a potent source of antibacterial and antifungal biomolecules. Both the target pathogens, bacteria (Escherischia coli, Klebsiella pneumoniae, and Acinetobacter baumannii) and fungi (Candida albicans, C. tropicalis, and Cryptococus sp.) were WHO prioritized. The bioassay guided approach led us to evaluate antibacterial and antifungal lead molecule(s) from an array of compounds using spectroscopic and in silico studies. The methanol derived crude extract was purified via thin layer chromatography (TLC) using solvent system methanol: chloroform (1:19). Maximum antimicrobial activity was observed in fractions D5, D6 and D7, the components of which were then recognized using high resolution-liquid chromatography/mass spectroscopy (Orbitrap) (HR-LC/MS). The screened compounds were then docked with target enzymes sterol-14-alpha demethylase and OmpF porin protein. The energy scores revealed that amongst all, lariciresinol-4-O-glucoside showed better binding affinity, in silico, using the Schrödinger Maestro 2018-1 platform. The 3-dimensional crystal structures of both the proteins were retrieved from the protein data bank (PDB), and showed binding energies of −14.35 kcal/mol, and −11.0 kcal/mol against respective drug targets. The molecular dynamics (MD) simulations were performed for 100 ns, using Desmond package, Schrödinger to evaluate the conformational stability and alteration of protein-ligand complexes during the simulation. Thus, our findings confirmed that lariciresinol-4-O-glucoside, a lignan derivative and known strong antioxidant, may be used as an important “lead” molecule to be developed as antibacterial and antifungal drugs in the future. Communicated by Ramaswamy H. Sarma. © 2022 Informa UK Limited, trading as Taylor & Francis Group.
Lead optimization based design, synthesis, and pharmacological evaluation of quinazoline derivatives as multi-targeting agents for Alzheimer's disease treatment
(Elsevier Masson s.r.l., 2024) Akash Verma; Digambar Kumar Waiker; Neha Singh; Abhinav Singh; Poorvi Saraf; Bhagwati Bhardwaj; Pradeep Kumar; Sairam Krishnamurthy; Saripella Srikrishna; Sushant Kumar Shrivastava
The complexity and multifaceted nature of Alzheimer's disease (AD) have driven us to further explore quinazoline scaffolds as multi-targeting agents for AD treatment. The lead optimization strategy was utilized in designing of new series of derivatives (AK-1 to AK-14) followed by synthesis, characterization, and pharmacological evaluation against human cholinesterase's (hChE) and β-secretase (hBACE-1) enzymes. Amongst them, compounds AK-1, AK-2, and AK-3 showed good and significant inhibitory activity against both hAChE and hBACE-1 enzymes with favorable permeation across the blood-brain barrier. The most active compound AK-2 revealed significant propidium iodide (PI) displacement from the AChE-PAS region and was non-neurotoxic against SH-SY5Y cell lines. The lead molecule (AK-2) also showed Aβ aggregation inhibition in a self- and AChE-induced Aβ aggregation, Thioflavin-T assay. Further, compound AK-2 significantly ameliorated Aβ-induced cognitive deficits in the Aβ-induced Morris water maze rat model and demonstrated a significant rescue in eye phenotype in the Aꞵ-phenotypic drosophila model of AD. Ex-vivo immunohistochemistry (IHC) analysis on hippocampal rat brains showed reduced Aβ and BACE-1 protein levels. Compound AK-2 suggested good oral absorption via pharmacokinetic studies and displayed a good and stable ligand-protein interaction in in-silico molecular modeling analysis. Thus, the compound AK-2 can be regarded as a lead molecule and should be investigated further for the treatment of AD. © 2024 Elsevier Masson SAS
Novel 5,6-diphenyl-1,2,4-triazine-3-thiol derivatives as dual COX-2/5-LOX inhibitors devoid of cardiotoxicity
(Academic Press Inc., 2022) Poorvi Saraf; Prabhash Nath Tripathi; Manish Kumar Tripathi; Avanish Tripathi; Himanshu Verma; Digambar Kumar Waiker; Royana Singh; Sushant Kumar Shrivastava
A novel series of 5,6-diphenyl-1,2,4-triazine-3-thiol derivatives were designed, synthesized, and screened for their inhibitory potential against COX-2 and 5-LOX enzymes. The compounds from the series have shown moderate to excellent inhibitory potential against both targets. Compound 6k showed the inhibitions against COX-2 (IC50 = 0.33 ± 0.02 μM) and 5-LOX inhibition (IC50 = 4.90 ± 0.22 μM) which was better than the standard celecoxib (IC50 = 1.81 ± 0.13 μM) for COX-2 and zileuton (IC50 = 15.04 ± 0.18 μM) for 5-LOX respectively. Further investigation on the selected derivative 6k in rat paw edema models revealed significant anti-inflammatory efficacy. Compound 6k has also shown negligible ulcerogenic liability as compared to indomethacin. Moreover, in vivo biochemical analysis also established the compound's antioxidant properties. Compounds 6c and 6k were also observed to be devoid of cardiotoxicity post-myocardial infarction in rats. The molecular docking and dynamics simulation studies of the most active derivative 6k affirmed their consentient binding interactions with COX-2 specific ravine and cleft of 5-LOX. © 2022
Novel Molecular Hybrids of N-Benzylpiperidine and 1,3,4-Oxadiazole as Multitargeted Therapeutics to Treat Alzheimer's Disease
(American Chemical Society, 2019) Piyoosh Sharma; Avanish Tripathi; Prabhash Nath Tripathi; Saumitra Sen Singh; Surya Pratap Singh; Sushant Kumar Shrivastava
Multitargeted hybrids of N-benzylpiperidine and substituted 5-phenyl-1,3,4-oxadiazoles were designed, synthesized, and evaluated against Alzheimer's disease (AD). Tested compounds exhibited moderate to excellent inhibition against human acetylcholinesterase (hAChE), butyrylcholinesterase (hBChE), and beta-secretase-1 (hBACE-1). The potential leads 6g and 10f exhibited balanced inhibitory profiles against all the targets, with a substantial displacement of propidium iodide from the peripheral anionic site of hAChE. Hybrids 6g and 10f also elicited favorable permeation across the blood-brain barrier and were devoid of neurotoxic liability toward SH-SY5Y neuroblastoma cells. Both leads remarkably disassembled Aβ aggregation in thioflavin T-based self- and AChE-induced experiments. Compounds 6g and 10f ameliorated scopolamine-induced cognitive dysfunctions in the Y-maze test. The ex vivo studies of rat brain homogenates established the reduced AChE levels and antioxidant activity of both compounds. Compound 6g also elicited noteworthy improvement in Aβ-induced cognitive dysfunctions in the Morris water maze test with downregulation in the expression of Aβ and BACE-1 proteins corroborated by Western blot and immunohistochemical analysis. The pharmacokinetic study showed excellent oral absorption characteristics of compound 6g. The in silico molecular docking and dynamics simulation studies of lead compounds affirmed their consensual binding interactions with PAS-AChE and aspartate dyad of BACE-1. © 2019 American Chemical Society.
Synthesis, cytotoxic evaluation, docking and in silico pharmacokinetic prediction of 4-arylideneamino/cycloalkylidineamino 1, 2-naphthoquinone thiosemicarbazones
(2013) Shubhanjali Shukla; Radhey Shyam Srivastava; Sushant Kumar Shrivastava; Ajit Sodhi; Pankaj Kumar
In an attempt to develop potent anticancer agents, a series of 4-arylideneamino/cycloalkylidineamino-1, 2-naphthoquinone thiosemicarbazones were synthesized and characterized using FT-IR, 1H NMR, 13C NMR spectroscopy and elemental analysis. The compounds were screened for antiproliferative activity against three human cancer cell lines (Hep-G2, MG-63 and MCF-7) using the MTT assay. Significant anticancer activity was observed for several members of the series. The compounds 4-(3, 4, 5-trimethoxybenzylidene amino) 1, 2-naphthoquinone-2-thiosemicarbazone (TS10) and 4-(4-hydroxy-3-methoxy benzylideneamino) 1, 2-naphthoquinone-2- thiosemicarbazone (TS13) were active cytotoxic agents in all three cancer cell lines, with IC50 values in the range of 3.5-6.4 μM. Further evaluation of some of these potent cytotoxic compounds demonstrated their good safety profile in a normal cell line (MCF-12A). Docking experiments showed a good correlation between the predicted glide scores and the IC50 values of these compounds. In silico ADME studies revealed that these compounds can be used for second generation development. © 2013 Informa UK, Ltd.