National Institute of Pharmaceutical Education and Research, Hyderabad

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Thummuri D.,National Institute of Pharmaceutical Education and Research, Hyderabad | Naidu V.G.M.,National Institute of Pharmaceutical Education and Research, Hyderabad | Naidu V.G.M.,National Institute of Pharmaceutical Education and Research, Guwahati | Chaudhari P.,Advanced Center for Treatment
Journal of Molecular Medicine | Year: 2017

Abstract: Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor, which plays an important role in the cellular defense against oxidative stress by induction of anti-oxidant and cytoprotective enzymes. In the current study, we sought to investigate the osteoprotective effect of carnosic acid (CA), a phenolic (catecholic) diterpene. It is widely identified for its electrophilic nature under oxidative stress conditions and thus anticipated to counter osteoporosis by facilitation of Nrf2 signalling. Osteoclast differentiation was induced by incubation of RAW 264.7 (mouse macrophage) cells and mouse bone marrow macrophages (BMMs) in the presence of receptor activator of NF-κB ligand (RANKL) (100 ng/ml). After treatment, osteoclastogenesis was assessed using tartrate-resistant acid phosphatase (TRAP) assay. We observed that 6 h pretreatment with CA (1.25, 2.5, 5 μM) decreased RANKL-induced osteoclast formation and abolished RANKL-induced ROS generation by activating Nrf2 and its transcriptional targets. Further, CA also inhibited RANKL-induced activation of NF-κB and MAPK signalling. RANKL-induced mRNA expression of osteoclast related genes and transcription factors was also diminished by CA. In vivo osteolysis was developed in C57BL/6 male mice using lipopolysaccharide (LPS). Consistent with in vitro results, in vivo μ-CT analysis of femurs showed that bone mineral density (BMD), bone mineral content (BMC), and bone architecture parameters such as trabecular thickness (Tb.Th) and trabecular space (Tb.Sp) were positively modulated by CA in LPS-injected mice. The results obtained in this study support that CA inhibits RANKL-induced osteoclastogenesis by maintaining redox homeostasis through modulation of Nrf2 and NF-κB pathways. Key Messages: Carnosic acid (CA) inhibits RANKL-induced osteoclastogenesis.CA inhibits RANKL-induced oxidative stress by upregulating Nrf2 transcriptional targets.CA attenuates RANKL-induced NF-κB and MAPK signalling activation.CA decreases NFATc1 and c-Fos expression.In vivo μ-CT analysis reveals that CA prevents bone loss in LPS-injected mice. © 2017 Springer-Verlag Berlin Heidelberg


Naveen C.,National Institute of Pharmaceutical Education and Research, Hyderabad | Naveen C.,Acharya Nagarjuna University | Tadikonda R.R.,Avanthi Institute of Pharmaceutical science
International Journal of Pharmacy and Pharmaceutical Sciences | Year: 2014

Objective: The present work was aimed at studying the effect of different non-volatile solvents used in the preparation of liquisolid compacts on the properties of tablets produced and dissolution rate of valsartan from the prepared tablets. Methods: The solvents selected for this purpose include propylene glycol, poly ethylene glycol 200, 600, Tween 20, and Tween 80. Avicel PH 102 was selected as a carrier, Aerosil 200 as a coating material and croscarmellose sodium as a disintegrant. The liquisolid tablets were prepared according to the mathematical model developed by Spireas and Bolton. The prepared tablets were evaluated for quality control tests like weight variation, uniformity of drug content, tablet hardness, friability test, disintegration and in vitro dissolution studies. In vitro dissolution studies were performed in 0.001 N HCl and compared with that of plain drug, marketed tablet and conventional tablets prepared by direct compression. Results: The FTIR studies indicated no significant interactions between drug and excipients. The physicochemical properties of the solvent affected tablet weight, hardness and friability. The dissolution studies did not show significant difference in the dissolution rate of valsartan. Conclusion: The amount of carrier material required to produce dry and free flowing powder depends on the viscosity of the non-volatile solvents where as the drug release was not significantly changed with type of non-volatile solvent.


Reddy C.N.,Indian Institute of Chemical Technology | Krishna N.H.,National Institute of Pharmaceutical Education and Research, Hyderabad | Reddy V.G.,Indian Institute of Chemical Technology | Alarifi A.,King Saud University | Kamal A.,National Institute of Pharmaceutical Education and Research, Hyderabad
Asian Journal of Organic Chemistry | Year: 2017

An unprecedented metal-free approach has been achieved for the synthesis of N-alkylated benzamides from phenacyl azides by oxidative cleavage of a C-C bond and formation of a new C-N bond in the presence of K2CO3. Various substituted phenacyl azides could be readily cleaved to access a variety of N-alkylated benzamides by using the new protocol, which is a viable alternative for the construction of amide bonds. This metal-free reaction forms amides in excellent yields with minimal generation of waste. The high functional group tolerance and diverse substrate scope make this reaction useful for organic synthesis. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


Begum S.,Malla Reddy Institute of Pharmaceutical science | Divya Bharathi K.,Malla Reddy Institute of Pharmaceutical science | Vaddepally L.,National Institute of Pharmaceutical Education and Research, Hyderabad | Tulja Rani G.,Malla Reddy Institute of Pharmaceutical science
Der Pharmacia Lettre | Year: 2014

A simple, specific and fast reverse phase liquid chromatographic method is established for determination of moxifloxacin hydrochloride and ketorolac tromethamine in bulk drugs and pharmaceutical formulations. Chromatographic separations for separation of moxifloxacin hydrochloride and ketorolac tromethamine were achieved within 8 minutes by use of Inertsil ODS-3V C8 column (250 X 4.6 mm, 5 μm) as stationary phase with mobile phase containing 10 mM potassium dihydrogen phosphate buffer with triethylamine (pH 3.5±0.05 adjusted with dilute phosphoric acid) acetonitrile and methanol (40:30:30 v/v/v) at a flow rate of 1.0 ml/ min-. Detection was performed at 306 nm using Prominance UV-Visible detector. The method was validated in accordance with ICH guidelines. Response was a linear function of concentrations over the range of 60-140 μg/ ml for moxifloxacin hydrochloride and 48-112 μg/ ml for ketorolac tromethamine. Limit of quantification (LOQ) was found to be 5.89, 5.29 and limit of detection (LOD) 1.94, 1.75 μg /ml for moxifloxacin hydrochloride and ketorolac tromethamine respectively. Accuracy and precision values of both within run and between-run obtained from six different sets of three quality control (QC) samples analyzed in separate occasions for both the analytes ranged from 98.98% to 100.04% respectively. The developed and validated method was successfully applied to quantitative determination of moxifloxacin hydrochloride and ketorolac tromethamine in pharmaceutical formulation.


Areti A.,National Institute of Pharmaceutical Education and Research, Hyderabad | Yerra V.G.,National Institute of Pharmaceutical Education and Research, Hyderabad | Naidu V.G.M.,National Institute of Pharmaceutical Education and Research, Hyderabad | Kumar A.,National Institute of Pharmaceutical Education and Research, Hyderabad
Redox Biology | Year: 2014

Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN) remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy. © 2014 The Authors.


Narva S.,Birla Institute of Technology and Science | Chitti S.,Birla Institute of Technology and Science | Bala B.R.,Indian Institute of Chemical Technology | Alvala M.,National Institute of Pharmaceutical Education and Research, Hyderabad | And 2 more authors.
European Journal of Medicinal Chemistry | Year: 2016

A series of thirty two novel pyrrolo[2,3-b]pyridine analogues synthesized, characterized (1H NMR, 13C NMR and MS) and cytotoxic evaluation of these molecules carried out over a panel of three human cancer cell lines including A549 (lung cancer), HeLa (cervical cancer) and MDA MB-231 (breast cancer), using sulforhodamine B assay method. Few molecules such as 5c, 5d, 5e, 5h, 5k, 5m, 5n, 5q, 5r, 7f, 7j, 7g and 7k exhibited maximum growth inhibitory action against the tested cancer cell lines at lower micro molar concentration. Noticeably, compounds exhibited good growth inhibition in all three cancer cell lines in the range of 0.12 μM-9.84 μM. Further study exposed that one of the active compound 5d could efficiently intercalate into calf thymus DNA to form 5d-DNA complex which might block DNA replication to influence their antiproliferative activity. The molecular interactions of all the synthesized analogs were also supported by molecular docking simulations. We believe that further optimization of these compounds will lead to potential anticancer agents. © 2016 Elsevier Masson SAS. All rights reserved.


Mallavadhani U.V.,Indian Institute of Chemical Technology | Prasad C.V.,Indian Institute of Chemical Technology | Shrivastava S.,National Institute of Pharmaceutical Education and Research, Hyderabad | Naidu V.G.M.,National Institute of Pharmaceutical Education and Research, Hyderabad
European Journal of Medicinal Chemistry | Year: 2014

Six novel 5,6-fused hybrids such as dihydrobenzofuran-quinone (4a and 4b), benzofuran-quinone (5a and 5b) and chromene-quinone (6a and 6b) of juglone based 1,4-naphthoquinones were synthesized by employing a three step protocol with the cyclisation of o-allyl phenol as the key step. The anticancer activity of the newly synthesized compounds was evaluated in vitro against seven human cancer cell lines including cervix (ME-180 and HeLa), breast (MCF-7, MDA-MB-453 and MDA-MB-231), prostate (PC-3) and colon (HT-29) by using MTT assay. The screening results showed that majority of the synthesized compounds exhibited significant anticancer activity. In particular, compounds 6a and 6b showed potent activities than the standard drug etoposide against prostate and breast cancer cell lines respectively. Flow cytometric analysis revealed that compounds 6a and 6b induced apoptosis and arrested the cell cycle at G2/M phase in PC-3 and MDA-MB-453 cells respectively. © 2014 Elsevier Masson SAS. All rights reserved.


PubMed | Indian Institute of Chemical Technology, National Institute of Pharmaceutical Education and Research, Hyderabad and Birla Institute of Technology and Science
Type: | Journal: European journal of medicinal chemistry | Year: 2016

A series of thirty two novel pyrrolo[2,3-b]pyridine analogues synthesized, characterized ((1)H NMR, (13)C NMR and MS) and cytotoxic evaluation of these molecules carried out over a panel of three human cancer cell lines including A549 (lung cancer), HeLa (cervical cancer) and MDA MB-231 (breast cancer), using sulforhodamine B assay method. Few molecules such as 5c, 5d, 5e, 5h, 5k, 5m, 5n, 5q, 5r, 7f, 7j, 7g and 7k exhibited maximum growth inhibitory action against the tested cancer cell lines at lower micro molar concentration. Noticeably, compounds exhibited good growth inhibition in all three cancer cell lines in the range of 0.12M-9.84M. Further study exposed that one of the active compound 5d could efficiently intercalate into calf thymus DNA to form 5d-DNA complex which might block DNA replication to influence their antiproliferative activity. The molecular interactions of all the synthesized analogs were also supported by molecular docking simulations. We believe that further optimization of these compounds will lead to potential anticancer agents.


PubMed | Indian Institute of Chemical Technology and National Institute of Pharmaceutical Education and Research, Hyderabad
Type: | Journal: European journal of medicinal chemistry | Year: 2014

Six novel 5,6-fused hybrids such as dihydrobenzofuran-quinone (4a and 4b), benzofuran-quinone (5a and 5b) and chromene-quinone (6a and 6b) of juglone based 1,4-naphthoquinones were synthesized by employing a three step protocol with the cyclisation of o-allyl phenol as the key step. The anticancer activity of the newly synthesized compounds was evaluated invitro against seven human cancer cell lines including cervix (ME-180 and HeLa), breast (MCF-7, MDA-MB-453 and MDA-MB-231), prostate (PC-3) and colon (HT-29) by using MTT assay. The screening results showed that majority of the synthesized compounds exhibited significant anticancer activity. In particular, compounds 6a and 6b showed potent activities than the standard drug etoposide against prostate and breast cancer cell lines respectively. Flow cytometric analysis revealed that compounds 6a and 6b induced apoptosis and arrested the cell cycle at G2/M phase in PC-3 and MDA-MB-453 cells respectively.


PubMed | National Institute of Pharmaceutical Education and Research, Hyderabad
Type: | Journal: Redox biology | Year: 2014

Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN) remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy.

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