17 results on '"V. G. M. Naidu"'
Search Results
2. Gold-capsuled polymeric nanomedicine for synergistic breast cancer photo-chemotherapy
- Author
-
Navneet Kaur, Eswara Rao Puppala, Rohit Srivastava, V. G. M. Naidu, and Asifkhan Shanavas
- Subjects
Modeling and Simulation ,General Materials Science ,Bioengineering ,General Chemistry ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics - Published
- 2022
3. Synthesis and Cytotoxic Activity of 1,2,4-Triazolo-Linked
- Author
-
Prasanna A, Yakkala, Samir R, Panda, Syed, Shafi, V G M, Naidu, M Shahar, Yar, Philemon N, Ubanako, Samson A, Adeyemi, Pradeep, Kumar, Yahya E, Choonara, Eugene V, Radchenko, Vladimir A, Palyulin, and Ahmed, Kamal
- Subjects
Tankyrases ,Phosphatidylinositol 3-Kinases ,Molecular Structure ,Cell Line, Tumor ,Humans ,Antineoplastic Agents ,Apoptosis ,Fluorouracil ,Drug Screening Assays, Antitumor ,Reactive Oxygen Species ,beta Catenin ,Cell Proliferation - Abstract
A series of new 1,2,4-triazolo-linked
- Published
- 2022
4. Piperine Attenuates Cigarette Smoke-Induced Oxidative Stress, Lung Inflammation, and Epithelial-Mesenchymal Transition by Modulating the SIRT1/Nrf2 Axis
- Author
-
Pritam Saha, Sneha Durugkar, Siddhi Jain, P. A. Shantanu, Samir R. Panda, Aishwarya Jala, Sharad Gokhale, Pawan Sharma, and V. G. M. Naidu
- Subjects
Mice, Inbred BALB C ,Epithelial-Mesenchymal Transition ,Organic Chemistry ,inflammation ,EMT ,piperine ,cigarette smoke ,airway disease ,antioxidant ,General Medicine ,Pneumonia ,GA-Binding Protein Transcription Factor ,Catalysis ,Antioxidants ,Computer Science Applications ,Inorganic Chemistry ,Mice ,Oxidative Stress ,Sirtuin 1 ,Tobacco ,Animals ,Physical and Theoretical Chemistry ,Molecular Biology ,Lung ,Spectroscopy - Abstract
Piperine (PIP) is a major phytoconstituent in black pepper which is responsible for various pharmacological actions such as anti-inflammatory, antioxidant, and antitumor activity. To investigate the effects and mechanisms of PIP on cigarette smoke (CS)-induced lung pathology using both in-vitro and in-vivo models. BEAS-2B and A549 cells were exposed to CS extract (CSE) for 48 h; BALB/c mice were exposed to CS (9 cigarettes/day, 4 days) to induce features of airway disease. PIP at doses of (0.25, 1.25, and 6.25 µM, in vitro; 1 and 10 mg/kg, in vivo, i.n) and DEX (1 µM, in vitro; 1 mg/kg, in vivo, i.n) were used to assess cytotoxicity, oxidative stress, epithelial–mesenchymal transition (EMT), Sirtuin1 (SIRT1), inflammation-related cellular signaling, and lung function. PIP treatment protects cells from CSE-induced lung epithelial cell death. PIP treatment restores the epithelial marker (p < 0.05) and decreases the mesenchymal, inflammatory markers (p < 0.05) in both in vitro and in vivo models. The PIP treatment improves the altered lung function (p < 0.05) in mice induced by CS exposure. Mechanistically, PIP treatment modulates SIRT1 thereby reducing the inflammatory markers such as IL-1β, IL-6 and TNF-α (p < 0.05) and enhancing the epigenetic marker HDAC2 (p < 0.05) and antioxidant marker Nrf2 (p < 0.05) expressions. Thus, PIP alleviates pulmonary inflammation by modulating the SIRT1-mediated inflammatory cascade, inhibits EMT, and activates Nrf2 signaling.
- Published
- 2022
5. Emerging trends in microneedle-based drug delivery strategies for the treatment of rheumatoid arthritis
- Author
-
Srividya Gorantla, Unnati Batra, Samshritha RN, Eswara Rao Puppala, Tejashree Waghule, V. G. M. Naidu, and Gautam Singhvi
- Subjects
Arthritis, Rheumatoid ,Drug Delivery Systems ,Microinjections ,Pharmaceutical Preparations ,Needles ,Pharmaceutical Science ,Humans ,Administration, Cutaneous ,Skin - Abstract
The current drug therapies for treating rheumatoid arthritis (RA) include nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, or biological products designed to mitigate the symptoms of the disease. These therapies with conventional delivery systems possess limitations such as lack of selectivity and adverse effects in the extra-articular tissues. Microneedles-based transdermal drug delivery gained huge attention that can overcome the limitations associated with conventional preparations.This review aims to provide detailed information on types of microneedles (MNs) and their usage in drug delivery for the management of RA. In addition, it also provides evidence for the effective use of MNs in RA treatment. Various types of MNs, their regulatory status, clinical trials, and patents are also compiled in this review.Microneedles are small patch-like structures consisting of needles in micron range arranged in array-like structure used to manage drugs designed to be given via transdermal route. Microneedles provide painless delivery, fast onset of action, bypass the first-pass metabolism, and be easily self-administered. In the case of RA treatment, which requires a long-term application of drugs, MN is a new and emerging way to ease the symptoms of RA.
- Published
- 2022
6. An Overview of the Heterogeneity of Major Depressive Disorder: Current Knowledge and Future Prospective
- Author
-
Mangala Lahkar, Sikta Bandopadhyay, V G M Naidu, Sumana Chakravarty, Kaipuzha Venu Athira, and Pavan Kumar Samudrala
- Subjects
MDD ,Disease ,Stress ,hypothalamic-pituitary-adrenal axis ,Epigenesis, Genetic ,Neuropharmacology ,Quality of life (healthcare) ,Stress, Physiological ,Neurotrophic factors ,medicine ,Animals ,Humans ,genetics ,Pharmacology (medical) ,neurotrophic factor ,Depression (differential diagnoses) ,Pharmacology ,Depressive Disorder, Major ,Modalities ,epigenetics ,business.industry ,Mechanism (biology) ,Brain ,General Medicine ,medicine.disease ,immune system ,Psychiatry and Mental health ,Neurology ,Major depressive disorder ,Neurology (clinical) ,business ,Neuroscience ,Stress, Psychological ,Pharmacogenetics ,neurotransmitter - Abstract
Major depressive disorder (MDD) is estimated to impose maximum debilitating effects on the society by 2030, with its critical effects on health, functioning, quality of life and concomitant high levels of morbidity and mortality. Yet, the disease is inadequately understood, diagnosed and treated. Moreover, with the recent drastic rise in the pace of life, stress has materialized as one of the most potent environmental factors for depression. In this scenario, it is important to understand the modern pathogenetic hypotheses and mechanisms, and possibly try to shift from the traditional approaches in depression therapy. These include the elaboration of pathophysiological changes in heterogeneous systems such as genetic, epigenetic, serotonergic, noradrenergic, gammaaminobutyric acid, glutamatergic and endocannabinoid systems, neurotrophic factors, HPA axis, immune system as well as cellular stress mechanisms. These components interact with each other in a complex matrix and further elucidation of their mechanism and cascade pathways are needed. This might aid in the identification of MDD subtypes as well as the development of sophisticated biomarkers. Further, characterization might also aid in developing multitargeted therapies that hold much promise as compared to the conventional monoamine based treatment. New candidate pharmacons, refined psychotherapeutic modalities, advanced neuro-surgical and imaging techniques as well as the implementation of pharmacokinetic, pharmacogenetic prescribing guidelines constitute the emerging expanses of MDD treatment.
- Published
- 2020
7. The Factors Influencing Gut Microbiota in Autoimmune Diseases
- Author
-
Syed Afroz Ali, Samir Ranjan Panda, Mangaldeep Dey, Ashok Kumar Datusalia, V. G. M. Naidu, and Rakesh Kumar Singh
- Published
- 2022
8. Polyphenolic-Rich Compounds From
- Author
-
Kalyani, Tene, M, Kalyan Kumar, G, Basveshwar, P, Eswara Rao, G, Jagadeesh Kumar, Pramod, Kumar, Deepak B, Pemmaraju, U S N, Murty, Ranadeep, Gogoi, and V G M, Naidu
- Subjects
Pharmacology ,dillenia pentagyna roxb ,cardioprotection ,oxidative stress ,ultrasonography ,doxorubicin ,Original Research - Abstract
Cardiovascular complications are the foremost concern in patients undergoing anticancer therapy. There is an unmet need to address the problems arising from the drug-induced toxicity for the long-term benefit of the patients undergoing chemotherapy. Alternative medicines are gaining their prosperity in addressing the various drug-induced organ toxicity. Dillenia pentagyna Roxb (DP) is an ethnomedicinal plant rich in flavonoids and phenolic contents. In India & Nepal, DP is a common ingredient of traditional medicines used to treat multiple ailments like inflammation, cancer, and diabetes. However, its protective role against doxorubicin (Dox) induced cardiotoxicity remains unexplored. Herein, we investigated the potential effects of various extracts/fractions obtained from the DP’s bark against Dox-induced cardiotoxicity, both in-vitro and in-vivo. The anti-oxidant content of the extracts/fractions was evaluated by using DPPH, ABTS and FRAP chemical assays. The results indicated that the hydroalcoholic (HA) extract of DP has intense anti-oxidant potential. Further fractionation of DP revealed that the phenolic-rich fraction (F1) has a high anti-oxidant potential. The protective effect of extract/fraction was also investigated in the H9c2 cell line following the Dox-induced cardiotoxicity model. We observed that the pre-treatment of extract/fraction in cardiomyocytes had exhibited increased cell viability. Fluorescence-based chemical assays indicated a decreased ROS levels in the treated groups in comparison to the Dox control group. The effect of DP was evaluated further in balb/c mice by the Dox-induced cardiotoxicity model. Non-invasive techniques like high-frequency ultrasonography and electrocardiogram revealed that the mice pre-treated with DP had improved cardiac functionality (left ventricular ejection fraction and stroke volume) and normalized the electrocardiograms compared to the Dox control group. Further, biochemical analysis with the cardiac tissues revealed that the cytoprotective proteins like HO-1, SOD-2, and Nrf-2 were elevated in the DP treated groups compared to the Dox control group. Overall, our results suggested that the bioactive extract/fractions of DP helped alleviate the Dox-induced cardiotoxicity. LC-QTOF-ESI-MS analysis of DP and F1 indicated that polyphenolic anti-oxidant compounds like gallic acid, syringic acid, and sinapic acid could be responsible for the potent -cardioprotective effect. Future understanding of the pharmacokinetics and pharmacodynamic parameters can help translate from the bench to the bedside.
- Published
- 2020
9. Forced degradation studies of lansoprazole using LC-ESI HRMS and 1 H-NMR experiments: in vitro toxicity evaluation of major degradation products
- Author
-
R. Srinivas, Narayana Nagesh, V. G. M. Naidu, G. Shankar, Roshan M. Borkar, U. Suresh, and L. Guntuku
- Subjects
Chromatography ,Chemistry ,010401 analytical chemistry ,Lansoprazole ,010402 general chemistry ,01 natural sciences ,High-performance liquid chromatography ,0104 chemical sciences ,chemistry.chemical_compound ,Hydrolysis ,Forced degradation ,medicine ,Degradation (geology) ,MTT assay ,Cytotoxicity ,Ammonium acetate ,Spectroscopy ,medicine.drug - Abstract
Regulatory agencies from all over the world have set up stringent guidelines with regard to drug degradation products due to their toxic effects or carcinogenicity. Lansoprazole, a proton-pump inhibitor, was subjected to forced degradation studies as per ICH guidelines Q1A (R2). The drug was found to degrade under acidic, basic, neutral hydrolysis and oxidative stress conditions, whereas it was found to be stable under thermal and photolytic conditions. The chromatographic separation of the drug and its degradation products were achieved on a Hiber Purospher, C18 (250 X 4.6mm, 5μ) column using 10 mM ammonium acetate and acetonitrile as a mobile phase in a gradient elution mode at a flow rate of 1.0 mL/min. The eight degradation products (DP1-8) were identified and characterized by UPLC/ESI/HRMS with in-source CID experiments combined with accurate mass measurements. DP-1, DP-2 and DP-3 were formed in acidic, DP-4 in basic, DP-5 in neutral and DP-1, DP-6, DP-7 and DP-8 were in oxidation stress condition Among eight degradation products, five were hitherto unknown degradation products. In addition, one of the major degradation products, DP-2 was isolated by using semi preparative HPLC and other two, DP-6 and DP-7 were synthesized. The cytotoxic effect of these degradation products (DP-2, DP-6 and DP-7) were tested on normal human cells such as HEK 293 (embryonic kidney cells) and RWPE-1(normal prostate epithelial cells) by MTT assay. From the results of cytotoxicity, it was found that lansoprazole as well as its degradation products (DP-2, DP-6 and DP-7) were nontoxic up to 50 μM concentrations and the latter showed slightly higher cytotoxicity when compared with that of lansoprazole. DNA binding studies using spectroscopic techniques indicate that DP-2, DP-6 and DP-7 molecules interact with ctDNA and may bind to its surface.
- Published
- 2017
10. DABCO-catalyzed one-pot three component synthesis of dihydropyrano[3,2-c]chromene substituted quinazolines and their evaluation towards anticancer activity
- Author
-
Sumathi Vodnala, V. G. M. Naidu, A. K. D. Bhavani, Promila, Ramakrishna Kamutam, and Ch. Prabhakar
- Subjects
Cell Survival ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,DABCO ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,Piperazines ,chemistry.chemical_compound ,Breast cancer cell line ,Catalytic Domain ,Cell Line, Tumor ,Drug Discovery ,Quinazoline ,Humans ,Organic chemistry ,Benzopyrans ,Molecular Biology ,Addition reaction ,Binding Sites ,010405 organic chemistry ,Chemistry ,Hydrogen bond ,Organic Chemistry ,Estrogen Receptor alpha ,Hydrogen Bonding ,Combinatorial chemistry ,0104 chemical sciences ,Molecular Docking Simulation ,4-Hydroxycoumarin ,Quinazolines ,Thermodynamics ,Molecular Medicine - Abstract
A facile DABCO promoted one-pot three component synthesis of a new series of C-C linked bis-heterocycle containing dihydropyrano[c]chromene as highly fused oxa-heteryl group at C-2 position of quinazoline was developed. Quinazoline-2-carbaldehyde, substituted 4-hydroxycoumarin and ethyl cyanoacetate were used as key components in the Knoevenagel-Michael addition reaction to get the titled compounds. These compounds were screened for anti-cancer activity against the breast cancer cell lines of MDA-MB 231, and MDA-MB 453.
- Published
- 2016
11. Corrigendum to 'Antidepressant activity of vorinostat is associated with amelioration of oxidative stress and inflammation in a corticosterone-induced chronic stress model in mice.' [Behav. Brain Res. 344 (2018) 73-84]
- Author
-
Mangala Lahkar, Rajaram Mohanrao Madhana, Swapnil Sinha, Indu Chandran Js, Athira Kv, and V G M Naidu
- Subjects
business.industry ,Inflammation ,Pharmacology ,medicine.disease_cause ,Behavioral Neuroscience ,chemistry.chemical_compound ,chemistry ,Corticosterone ,Medicine ,Antidepressant ,Chronic stress ,medicine.symptom ,business ,Vorinostat ,Oxidative stress ,medicine.drug - Published
- 2018
12. Synthesis and characterization of new s-triazine bearing benzimidazole and benzothiazole derivatives as anticancer agents
- Author
-
G. Jagadeesh Kumar, S. Naveen Kumar, Dinesh Thummuri, Lavanya Bindu Sree Adari, V. G. M. Naidu, Kolupula Srinivas, and V. Jayathirtha Rao
- Subjects
Organic Chemistry ,General Pharmacology, Toxicology and Pharmaceutics - Published
- 2015
13. Antidepressant activity of vorinostat is associated with amelioration of oxidative stress and inflammation in a corticosterone-induced chronic stress model in mice
- Author
-
V G M Naidu, Athira K, Indu Chandran Js, Rajaram Mohanrao Madhana, Swapnil Sinha, and Mangala Lahkar
- Subjects
0301 basic medicine ,Male ,endocrine system ,medicine.medical_specialty ,Anti-Inflammatory Agents ,Anxiety ,medicine.disease_cause ,Hydroxamic Acids ,Hippocampus ,Antioxidants ,03 medical and health sciences ,Behavioral Neuroscience ,chemistry.chemical_compound ,Mice ,Random Allocation ,0302 clinical medicine ,Corticosterone ,Internal medicine ,Fluoxetine ,medicine ,Animals ,Chronic stress ,Vorinostat ,Inflammation ,Depressive Disorder ,business.industry ,medicine.disease ,Malondialdehyde ,Antidepressive Agents ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,chemistry ,Chronic Disease ,Major depressive disorder ,Antidepressant ,business ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,Oxidative stress ,Stress, Psychological ,medicine.drug - Abstract
Major depressive disorder (MDD) is a multifactorial neuropsychiatric disorder. Chronic administration of corticosterone (CORT) to rodents is used to mimic the stress associated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, a well-established feature found in depressive patients. Recently, preclinical studies have demonstrated the antidepressant potential of histone deacetylase (HDAC) inhibitors. So, we examined the antidepressant potential of vorinostat (VOR), a HDAC inhibitor against CORT injections in male mice. VOR (25 mg/kg; intraperitoneal) and fluoxetine (FLX) (15 mg/kg; oral) treatments were provided to CORT administered mice. At the end of dosing schedule, neurobehavioral tests were conducted; followed by mechanistic evaluation through biochemical analysis, RTPCR and western blot in serum and hippocampus. Neurobehavioral tests revealed the development of anxiety/depressive-like behavior in CORT mice as compared to the vehicle control. Depressive-mice showed concomitant HPA axis dysregulation as observed from the significant increase in serum CORT and ACTH. Chronic CORT administration was found to significantly increase hippocampal malondialdehyde (MDA) and iNOS levels while lowering glutathione (GSH) content, as compared to vehicle control. VOR treatment, in a similar manner to the classical antidepressant FLX, significantly ameliorated anxiety/depressive-like behavior along with HPA axis alterations induced by CORT. The antidepressant-like ability of drug treatments against chronic CORT induced stress model, as revealed in our study, may be due to their potential to mitigate inflammatory damage and oxidative stress via modulation of hippocampal NF-κB p65, COX-2, HDAC2 and phosphorylated JNK levels.
- Published
- 2017
14. Forced degradation studies of lansoprazole using LC-ESI HRMS and
- Author
-
G, Shankar, R M, Borkar, U, Suresh, L, Guntuku, V G M, Naidu, N, Nagesh, and R, Srinivas
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Hot Temperature ,Magnetic Resonance Spectroscopy ,Photolysis ,Cell Survival ,Tandem Mass Spectrometry ,Hydrolysis ,Humans ,Lansoprazole ,Proton Pump Inhibitors ,Oxidation-Reduction ,Chromatography, High Pressure Liquid ,Cell Line - Abstract
Regulatory agencies from all over the world have set up stringent guidelines with regard to drug degradation products due to their toxic effects or carcinogenicity. Lansoprazole, a proton-pump inhibitor, was subjected to forced degradation studies as per ICH guidelines Q1A (R2). The drug was found to degrade under acidic, basic, neutral hydrolysis and oxidative stress conditions, whereas it was found to be stable under thermal and photolytic conditions. The chromatographic separation of the drug and its degradation products were achieved on a Hiber Purospher, C18 (250 × 4.6 mm, 5 μ) column using 10 mM ammonium acetate and acetonitrile as a mobile phase in a gradient elution mode at a flow rate of 1.0 ml/min. The eight degradation products (DP1-8) were identified and characterized by UPLC/ESI/HRMS with in-source CID experiments combined with accurate mass measurements. DP-1, DP-2 and DP-3 were formed in acidic, DP-4 in basic, DP-5 in neutral and DP-1, DP-6, DP-7 and DP-8 were in oxidation stress condition Among eight degradation products, five were hitherto unknown degradation products. In addition, one of the major degradation products, DP-2, was isolated by using semi preparative HPLC and other two, DP-6 and DP-7 were synthesized. The cytotoxic effect of these degradation products (DP-2, DP-6 and DP-7) were tested on normal human cells such as HEK 293 (embryonic kidney cells) and RWPE-1(normal prostate epithelial cells) by MTT assay. From the results of cytotoxicity, it was found that lansoprazole as well as its degradation products (DP-2, DP-6 and DP-7) were nontoxic up to 50-μM concentrations, and the latter showed slightly higher cytotoxicity when compared with that of lansoprazole. DNA binding studies using spectroscopic techniques indicate that DP-2, DP-6 and DP-7 molecules interact with ctDNA and may bind to its surface. Copyright © 2017 John WileySons, Ltd.
- Published
- 2017
15. ChemInform Abstract: DABCO-Catalyzed One-Pot Three Component Synthesis of Dihydropyrano[3,2-c]chromene Substituted Quinazolines and Their Evaluation Towards Anticancer Activity
- Author
-
Promila Promila, A. K. D. Bhavani, Ch. Prabhakar, V. G. M. Naidu, Ramakrishna Kamutam, and Sumathi Vodnala
- Subjects
chemistry.chemical_compound ,chemistry ,Component (thermodynamics) ,Organic chemistry ,General Medicine ,DABCO ,Catalysis - Published
- 2016
16. Albumin anchored docetaxel lipid nanoemulsion for improved targeting efficiency - preparation, characterization, cytotoxic, antitumor and in vivo imaging studies
- Author
-
Veerabrahma Kishan, V. G. M Naidu, Syed Muzammil Afzal, and N. Harishankar
- Subjects
Materials science ,Sonication ,Chemistry, Pharmaceutical ,Pharmaceutical Science ,02 engineering and technology ,Docetaxel ,030226 pharmacology & pharmacy ,HeLa ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Drug Delivery Systems ,In vivo ,Albumins ,Cell Line, Tumor ,medicine ,Zeta potential ,Animals ,Humans ,Drug Carriers ,Chromatography ,biology ,Albumin ,General Medicine ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Lipids ,Xenograft Model Antitumor Assays ,In vitro ,Mice, Inbred C57BL ,Cell culture ,Nanoparticles ,Taxoids ,0210 nano-technology ,medicine.drug - Abstract
The aim was to develop albumin anchored docetaxel lipid nanoemulsion (ALNE) for improving tumor targeted delivery. The O/W lipid nanoemulsion, LNEs were prepared by homogenization and ultrasonication processes. The size of globules and zeta potential were measured by Malvern Zetasizer. Albumin was coupled to stearylamine containing lipid nanoemulsion (SALNE) globules using water soluble EDC reaction. The drug content and entrapment efficiencies for the LNEs were determined by the high-performance liquid chromatography. The in vitro cytotoxic studies of the delivery systems were performed on MCF-7 and Hela cells. The IC 50 values of ALNE on both the cell lines were statistically significant. The in vivo antitumor activity was tested on solid tumors induced in C57BL/6 mice. This study revealed that the percentage tumor inhibition for the groups treated with DLNE, SALNE and ALNE when compared with untreated control was found to be 55.62 ± 5.41%, 54.27 ± 4.85% and 80.01 ± 2.74%, respectively. Furthermore, in vivo distribution studies were carried out in breast cancer MDA-MB231 xenografted Balb/c mice. The LNEs were loaded with fluorescent DiD oil and the distribution in different organs after 6 h was tracked using Caliper life sciences in vivo imaging system. The studies revealed that ALNE was superior in tumor targeting activity when compared with DLNE and SALNE by 3.04 and 2.26 folds, respectively. The average radiance values of ALNE on the tumor tissue were statistically significant when compared with DLNE, SALNE at p 0.01. In addition, this strategy can become a platform technology for other lipophilic drugs to target tumors.
- Published
- 2015
17. One-pot synthesis of podophyllotoxin-thiourea congeners by employing NH₂SO₃H/NaI: Anticancer activity, DNA topoisomerase-II inhibition, and apoptosis inducing agents
- Author
-
Nagula, Shankaraiah, Niggula Praveen, Kumar, Suresh Babu, Amula, Shalini, Nekkanti, Manish Kumar, Jeengar, V G M, Naidu, T Srinivasa, Reddy, and Ahmed, Kamal
- Subjects
Dose-Response Relationship, Drug ,Molecular Structure ,Sulfur Oxides ,Thiourea ,Antineoplastic Agents ,Apoptosis ,Sodium Iodide ,Amides ,Structure-Activity Relationship ,DNA Topoisomerases, Type II ,Cell Line, Tumor ,Humans ,Topoisomerase II Inhibitors ,Drug Screening Assays, Antitumor ,Cell Proliferation ,Podophyllotoxin - Abstract
A facile one-pot method for the synthesis of novel podophyllotoxin-thiourea congeners has been developed by using NH2SO3H/NaI system. Interestingly, 4β-azido podophyllotoxin reduction with concomitant aryl isothiocyanates coupling under mild reaction conditions has been achieved. These compounds have been investigated for their in vitro cytotoxicity against A549, MDA MB-231, DU-145, LNCaP, and HGC-27 cancer cell lines. Some of the representative compounds have selectively exhibited cytotoxicity on DU-145 (human prostate cancer) cells and the most potent compound was 4a (IC50 of 0.50 ± 0.03 μM) with optimal safety therapeutic window (81.7 fold) on normal human prostate cell line (RWPE-1, IC50 of 40.85 ± 0.78). The flow-cytometric analysis of the compound 4a in prostate cancer cells indicated a strong G2/M-phase arrest and significant topoisomerase II inhibition activity. Furthermore, these compounds induce apoptosis as observed by Acridine Orange and Ethidium Bromide (AO/EB) staining and Annexin V binding assay. Molecular docking results of the title compounds with topoisomerase-IIα were presented as theoretical support for the experimental data.
- Published
- 2015
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.