Publications by authors named "Shailaja Karri"

8 Publications

  • Page 1 of 1

Synthesis and anti-inflammatory activity of 2-oxo-2H-chromenyl and 2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates.

Bioorg Med Chem Lett 2020 08 10;30(16):127341. Epub 2020 Jun 10.

Department of Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; AcSIR-Postal Staff College Area, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh 201002, India. Electronic address:

Cycloaddition reaction of 4-chloro-2-oxo-2H-chromene-3-carbaldehydes (3a-g) and 4-chloro-2H-chromene-3-carbaldehydes (7a-h) with activated alkynes (4a-b) provided the 2-oxo-2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates (5a-n) and 2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates (8a-p). All the prepared compounds were screened for anti-inflammatory activity. In vitro anti-inflammatory activity data demonstrated that the compounds 5g, 5i, 5k-l and 8f are effective among the tested compounds against TNF-α (1.108 ± 0.002, 0.423 ± 0.022, 0.047 ± 0.001, 0.070 ± 0.002 and 0.142 ± 0.001 µM) in comparison with standard compound Prednisolone (0.033 ± 0.002 µM). Based on in vitro results, three compounds (5i, 5k and 8f) have been selected for in vivo experiments and these compounds are identified as better compounds with respect to anti-inflammatory activity in LPS induced mice model. Compound 5i was identified as potent and showed significant reduction in TNF-α and IL-6.
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http://dx.doi.org/10.1016/j.bmcl.2020.127341DOI Listing
August 2020

Potential Therapeutic Application of Zinc Oxide Nanoflowers in the Cerebral Ischemia Rat Model through Neuritogenic and Neuroprotective Properties.

Bioconjug Chem 2020 03 25;31(3):895-906. Epub 2020 Feb 25.

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India.

Neuritogenesis, a complex process of the sprouting of neurites, plays a vital role in the structural and functional restoration of cerebral ischemia-injured neuronal tissue. Practically, there is no effective long-term treatment strategy for cerebral ischemia in clinical practice to date due to several limitations of conventional therapies, facilitating the urgency to develop new alternative therapeutic approaches. Herein, for the first time we report that pro-angiogenic nanomaterials, zinc oxide nanoflowers (ZONF), exhibit neuritogenic activity by elevating mRNA expression of different neurotrophins, following PI3K/Akt-MAPK/ERK signaling pathways. Further, ZONF administration to global cerebral ischemia-induced Fischer rats shows improved neurobehavior and enhanced synaptic plasticity of neurons via upregulation of Neurabin-2 and NT-3, revealing their neuroprotective activity. Altogether, this study offers the basis for exploitation of angio-neural cross talk of other pro-angiogenic nano/biomaterials for future advancement of alternative treatment strategies for cerebral ischemia, where neuritogenesis and neural repair are highly critical.
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http://dx.doi.org/10.1021/acs.bioconjchem.0c00030DOI Listing
March 2020

Synthesis and biological evaluation of some novel 1,2,3-triazole hybrids of myrrhanone B isolated from Commiphora mukul gum resin: Identification of potent antiproliferative leads active against prostate cancer cells (PC-3).

Eur J Med Chem 2020 Feb 18;188:111974. Epub 2019 Dec 18.

Centre for Natural Products & Traditional Knowledge, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India. Electronic address:

A series of 28 novel 1,2,3-triazole hybrids of myrrhanone B have been designed and synthesized by employing regioselective Cu catalyzed Huisgen 1,3-dipolar cycloaddition reaction in highly efficient manner. All the synthesized analogues were assessed for their antiproliferative potential against A549 (Lung), DU145 (Prostate), MDA-MB-231 (Breast), SiHa (Cervical), U87MG (Glioblastoma), PC-3 (Prostate), HT-29 (Colon), L132 (Normal lung) cell lines. Further, the synthesized hybrids have also been screened for anti-inflammatory activity (TNF-α and IL-1β) and α-glucosidase inhibitory activity. The biological results revealed that compound 11 (meta hydroxy phenyl 1,2,3-triazole) and compound 29 (deoxyuridine 1,2,3-triazole) found to be the most potent antiproliferative ones against PC-3 cell line. Compound 11 (IC: 6.57 ± 0.62 μM) showed six folds more potent than parent compound 1 (IC: 40.67 ± 2.2 μM) and displayed almost identical inhibitory activity with standard doxorubicin (IC: 5.05 ± 0.25 μM), whereas compound 29 (IC: 10.85 ± 0.90 μM) exhibited four folds more potent than parent myrrhanone B (1). In view of potent activity of compounds 11 and 29 they have been subjected to detailed flowcytometry analysis. Compound 29 treated cells significantly increased the SubG1 population of cells indicative of apoptosis compared to compound 11. Further, the results of anti-inflammatory studies indicated that compounds 3, 6, 9, 27, 28, 29 and 30 exhibited significant inhibitory activity against both TNF-α and IL-1β than the parent compound 1. Interestingly, compound 27 exhibited good activity towards inflammatory cytokines TNF-α (IC: 7.83 ± 0.95 μM). Interestingly, α-glucosidase inhibitory assay results revealed that compounds 14 (IC: 2.77 ± 0.59 μM) and 16 (IC: 4.12 ± 0.77 μM) as the most potent ones. In fact, compound 14 exhibited highest activity and found to be several times more potent than the parent compound 1 as well as standard acarbose (IC: 2124 ± 170 μM).
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http://dx.doi.org/10.1016/j.ejmech.2019.111974DOI Listing
February 2020

Potent and Selective Cytotoxic and Anti-inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands.

Chemistry 2019 Nov 30;25(62):14089-14100. Epub 2019 Sep 30.

Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne, 3001, Australia.

Four cycloaurated phosphine sulfide complexes, [Au{κ -2-C H P(S)Ph } ][AuX ] [X=Cl (2), Br (3), I (4)] and [Au{κ -2-C H P(S)Ph } ]PF (5), have been prepared and thoroughly characterized. The compounds were found to be stable under physiological-like conditions and showed excellent cytotoxicity against a broad range of cancer cell lines and remarkable cytotoxicity in 3D tumor spheroids. Mechanistic studies with cervical cancer (HeLa) cells indicated that the cytotoxic effects of the compounds involve the inhibition of thioredoxin reductase and induction of apoptosis through mitochondrial disruption. In vivo experiments in nude mice bearing HeLa xenografts showed that treatment with compounds 4 and 5 resulted in significant inhibition of tumor growth (35.8 and 46.9 %, respectively), better than that of cisplatin (29 %). The newly synthesized gold complexes were also evaluated for their in vitro and in vivo anti-inflammatory activity through the study of lipopolysaccharide (LPS)-activated macrophages and carrageenan-induced hind paw edema in rats, respectively.
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http://dx.doi.org/10.1002/chem.201903388DOI Listing
November 2019

Synthesis of substituted biphenyl methylene indolinones as apoptosis inducers and tubulin polymerization inhibitors.

Bioorg Chem 2019 05 29;86:210-223. Epub 2019 Jan 29.

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi 110062, India. Electronic address:

A new series of biphenyl methylene indolinones has been designed, synthesized and evaluated for their in vitro antiproliferative activity against various cancer cell lines like DU-145 (prostate cancer cell line), 4T1 (mouse breast cancer cell line), MDA-MB-231 (human breast cancer cell line), BT-549 (human breast cancer cell line), T24 (human urinary bladder carcinoma cell line), and HeLa (cervical cancer cell line). Among the series, compound 10e showed potent in vitro cytotoxic activity against HeLa and DU-145 cancer cell lines with IC value of 1.74 ± 0.69 µM and 1.68 ± 1.06 µM respectively. To understand the underlying mechanism of most potent cytotoxic compound 10e, various mechanistic studies were carried out on DU-145 cell lines. Cell cycle analysis results revealed that these conjugates affect both G0/G1 and G2/M phase of the cycle, tubulin binding assay resulted that compound 10e interrupting microtubule network formation by inhibiting tubulin polymerization with IC value of 4.96 ± 0.05 μM. Moreover, molecular docking of 10e on colchicine binding site of the tubulin explains the interaction of 10e with tubulin. Clonogenic assay indicated inhibition of colony formation by compound 10e in a dose dependent manner. In addition, morphological changes were clearly observed by AO/EB and DAPI staining studies. Moreover, ROS detection using DCFDA, JC-1, and annexin V-FITC assays demonstrated the significant apoptosis induction by 10e.
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http://dx.doi.org/10.1016/j.bioorg.2019.01.063DOI Listing
May 2019

Design, synthesis, anti-inflammatory, cytotoxic and cell based studies of some novel side chain analogues of myrrhanones A & B isolated from the gum resin of Commiphora mukul.

Bioorg Chem 2019 02 23;82:306-323. Epub 2018 Oct 23.

Applied Biology Department, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.

Myrrhanones A (1) and B (2), isolated from the gum resin of Commiphora mukul, were reported to exhibit anticancer and anti-inflammatory activities. In view of their interesting skeletal features and biological activities they have been chemically modified by exploiting their side chain functionalities to synthesise 29 diverse analogues. All the synthesized analogues were screened for their cytotoxic potential against a panel of five human cancer cell lines which include DU145 (Prostate), HT-29 (Colon), MCF-7 (Breast), Hela (Cervical) and U87MG (Glioblastoma) along with a normal cell line (L132). The synthesized analogues were also screened for anti-inflammatory activity against TNF-α and IL-1β using LPS induced inflammation model employing U937 cells. The biological screening results revealed that compounds 4b (piperidine analogue), 9d (linear aliphatic four member amide analogue) and 9i (N-methyl piperazine analogue) displayed significant cytotoxic activity against MCF-7, HT-29 and DU145 [IC (μM): 4.65 ± 1.28, 5.48 ± 0.13 and 6.63 ± 1.39] respectively. These analogues were further taken up for apoptotic assay, which confirmed that compounds 4b, 9d and 9i induced apoptosis in MCF-7, HT-29, DU145 cells and arrested in G0/G1 phase. Further, compounds 9c and 9g found to exhibit good anti-inflammatory activity against TNF-α with IC (μM) values of 10.02 ± 2.13 and 10.53 ± 0.48 respectively, while compound 2 exhibited strong inhibitory activity against both TNF-α (IC: 9.39 ± 0.44 μM) and IL-1β (IC: 12.15 ± 1.36 μM).
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http://dx.doi.org/10.1016/j.bioorg.2018.10.039DOI Listing
February 2019

Curcumin inspired 2-chloro/phenoxy quinoline analogues: Synthesis and biological evaluation as potential anticancer agents.

Bioorg Med Chem Lett 2018 03 2;28(5):892-898. Epub 2018 Feb 2.

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India; School of Pharmaceutical Education and Research (SPER), Jamia Hamdard University, New Delhi 110062, India. Electronic address:

Synthesis of twenty new curcumin inspired 2-chloro/phenoxy quinoline derivatives is outlined in this study. The obtained new chemical entities were screened in vitro for their cytotoxic activity towards various tumor cell lines. Of the compounds screened, 6c and 9d exhibited significant activity and the most active analogue 6c displayed promising cytotoxicity against PC-3 (IC of 3.12 ± 0.11 μM), DU-145, NCI-H460 and 4 T1 cell lines. Further, 6c and 9d have 2.1 and 1.4 times more aqueous solubility, respectively, than curcumin. Additionally, the promising candidate 6c could induce G2/M cell cycle arrest and apoptosis in PC-3 cells, as determined by AO-EB staining, DAPI staining, analysis of ROS levels as well as annexin binding assay.
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http://dx.doi.org/10.1016/j.bmcl.2018.01.070DOI Listing
March 2018

A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic.

Sci Rep 2017 05 4;7(1):1492. Epub 2017 May 4.

Chemical Biology, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, 500007, India.

Following our recent discovery of a new scaffold exhibiting significant neurotrophic and neurogenic activities, a structurally tweaked analogue, embodying a 2-oxa-spiro [5.4]decane framework, has been conceptualised and found to be more potent and versatile. It exhibits enhanced neurotrophic and neurogenic action in in vitro, ex vivo and in vivo models and also shows robust neuroprotection in mouse acute cerebral stroke model. The observed attributes are traceable to the predominant activation of the TrkB-PI3K-AKT-CREB pathway. In addition, it also exhibits remarkable anti-neuroinflammatory activity by concurrently down-regulating pro-inflammatory cytokines IL-1α and IL-6, thereby providing a unique molecule with a trinity of neuroactivities, i.e. neurotrophic, neurogenic and anti-inflammatory. The new chemical entity disclosed here has the potential to be advanced as a versatile therapeutic molecule to treat stroke, depression, and possibly other neuropsychiatric disorders associated with attenuated neurotrophic/ neurogenic activity, together with heightened neuroinflammation.
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http://dx.doi.org/10.1038/s41598-017-01297-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431446PMC
May 2017
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