List of on-going Extramural Research Projects

Project Code

1. Gain insights into the mechanism of allosteric inhibition in PTP1B using MDS
1.1 Study interaction and energy aspects of binding, affinity and selectivity of allosteric inhibitors by performing comparative        molecular dynamics and binding free energy calculations on the PTP1B
1.2 Study the changes in the protein associated with the simultaneous binding of substrate and allosteric inhibitor at their respective site using molecular dynamics

2. Structure based and ligand based Pharmacophore model generations and virtual screening of libraries
2.1 Develop a dynamic receptor based pharmacophore from the conformations generated during molecular dynamic simulations for PTP1B
2.2 Develop a ligand based pharmacophore query using the shape of the reported allosteric inhibitors of PTP1B

3. Identification of potential hits and their validation
3.1 Carry out molecular dynamics and binding energy calculations for the selective hits obtained from virtual screening
3.2 Perform molecular docking studies

4. Crystallization aspect of PTP1B

1 To design and optimize novel molecules as allosteric site-directed PTP1B inhibitors using CADD methodologies
1.1 To understand the mechanism of allosteric inhibition of PTP1B
1.2 To develop ligand and receptor based pharmacophore models followed by database searching
1.3 To carry out molecular docking studies for database searched hits
1.4 To perform ADME/Toxicity analysis and rank potential hits.
1.5 To purchase the molecules designed and carry out in-vitro screening studies

2.To carry out protein crystallization

To select excipients based on the structural and physicochemical properties of drugs and to generate nanocrystalline dispersions of selected drugs by spray drying, by incorporating excipients to induce nanocrystallization

1 To perform the bioavailability study of selected drug and its NSD in experimental animals in order to assess the actual advantage obtained out of preparation of nanophases

2. To perform the thermodynamic and kinetic characterization of drug and assessment of its crystallization kinetics by various methods

3. To understand the molecular level mechanisms in the formation of NSD

1. Synthesis of azafluorenes and azafluorenones

2. A natural product, onychine containing azafluorenone core

3. Exploration of a methyloxycarbonyl derivative of azafluorene as amine protecting group

1.  Increasing OP-hydrolyzing activity of rSsoPox enzyme by random mutagenesis approach.

2.  Optimization of protocol(s) for production of rSsoPox enzymes and their biochemical characterization

3.  Generation and characterization of rSsoPox-immobilized nanobiocatalyst.

1.     Generation of NSDs of HRN with selected small molecule excipient(s) using spray drying process

2.     Mechanistic understanding on generation of NSD

3.     Biopharmaceutical properties of NSD

4.     In vivo breast cancer therapeutic activity of developed formulations in animal models

5.     Formulation development for oral route

1.     To study the role of the glycerol synthetic enzyme, Gpd1, in aggregation of mutant huntingtin in Saccharomyces cerevisiae

2.     To study the role of the glycerol transporter, Fps1, in aggregation of mutant huntingtin in Saccharomyces cerevisiae

3.     To study the effect of dietary restriction on aggregation of mutant huntingtin in Saccharomyces cerevisiae

1.     To perform QC studies on drugs to obtain their most stable conformation

2.     To assess physical and dynamical and structural properties

3.     To perform full atomistic simulations

4.     To carryout PFM analysis

5.     To perform QM/MM studies

1.   Preparation of extracts from roots

2.   Isolation and characterization of bioactive compounds from active extracts

3.   Quantification of active principles in the extracts

1.   Regulation of expression of mutant huntingtin-specific RNA aptamers in yeast cells

2.   Selective expression of RNA aptamers in yeast cells expressing mutant huntingtin fragment

3.   Effect of selected RNA aptamers on mutant huntingtin fragment expressed in neuronal cells

1.     To isolate, characterize and elucidate the structure of bioactive compounds possessing potential xanthine oxidase inhibitory activity

2.     Develop mass isolation protocol of pure compounds exhibiting XOI

1.     To rank order the efficacy of pharmacotherapeutic treatment options available for chronic low back pain using Bayesian multiple treatment comparison approach

2.     To rank order the safety of pharmacotherapeutic treatment options available for chronic low back pain using Bayesian multiple treatment comparison approach

3.    To assess the generalized cost- effectiveness of pharmacological treatments available for chronic low back pain using markov modeling

1.     To investigate role of epigenetic alteration such as global DNA methylation under insulin resistance conditions

2.     To study alteration in DNA methylation at the promoter of genes responsible for insulin resistance

3.     Investigation of impact of DNMT1 inhibitors and its therapeutic role in insulin resistance

1.   To study the influence of hyperglycemia on the genetic and epigenetic alterations in the testicular patho-physiology of rat.

2.   To investigate the role of genetic and epigenetic alterations in the zinc and selenium supplementation in the testicular patho-physiology during hyperglycemic condition in rat

3.   To explore the involvement of novel testicular markers (Nrf2) in hyperglycemia as well as supplementation conditions (Nrf2 activator) and to correlate the testicular damage as well as amelioration

1.   Identification of molecules having solubility limited oral bioavailability

2.   Generation of lab scale batches of nanocrystalline solid dispersion using NanoCrySP

3.   Performance evaluation of lab scale batches

4.   Scale-up of suitable prototype formulations under GMP conditions

1.     To create selected mutations in the sequence of M.tb GAPDH (Rv 1436)

2.     To express and purify individual mutant proteins

3.    To evaluate the effect of these mutant ions on the multifunctional properties of GAPDH (i.e Transferrin binding /Plasminogen binding)

1.     To determine whether the GAPDH-Transferrin complex recycled in M.tb cells.

2.     M.tb GAPDH may be secreted as a soluble protein or associated with bacterial vesicles.

3.     To assess whether intracellular M.tb secrete GAPDH out of the phagosome and whether it is relocated in the infected macrophage.

4.     To assess extracellular secretion of the protein from infected macrophages.

5.     Uptake of transferrin to the phagosome.

6.     Relevance of PTMs in GAPDH

1.     Coordination of network program.

2.     Development of processing and techniques to prepare specified extracts/fractions from SBT raw material received from IHBT.

3.     Creation of library of bioactive molecules from SBT for standardization purposes.

4.     Standardization of extracts using TLC/HPTLC, GC/GC-MS, HPLC, LC-MS and NMR.

5.     Evaluation of extracts, fractions, and oils for antioxidant activity.

6.     Evaluation of extracts, fractions, and oils for immunomodulatory activity.

7.     Evaluation of extracts, fractions, and oils for wound healing activity.

8.     Evaluation of extracts, fractions, and oils for anti-hyperlipidemic activity.

9.     Evaluation of extracts, fractions, and oils for anti-inflammatory activity.

10.  Evaluation of extracts, fractions, and oils for gastric ulcer preventing activity.

11.  Formulation studies on active fractions and extracts and development of NDDS for SBT.

12.  Evaluation of developed formulations for antioxidant and immunomodulatory activity, wound healing activity, antihyperlipidemic activity, anti-inflammatory and gastric ulcer preventing activity.

13.  Standardization, stability and bioavailability studies on formulations.

14.  Toxicity studies on the final product formulations.

1.     Development of lipidic prodrugs of amphotericin B with improved gastrointestinal stability and permeability therefore to enhance its oral bioavailability

2.     Encapsulation of lipidic prodrug of AmB in lipid based nanodrug delivery systems with high practical drug loading.

3.     To reduce hemolytic and nephrotoxicity of the amphotericin B

1.     To improve oral delivery of penicillin V

2.     Characterization of Benzathine penicillin G for its physicochemical properties

3.     To design an improved delivery system for Rheumatic Heart Disease (RHD) patients on options of- Designing a sustained release system

4.     Establishment of proof-of-concept of delivery profile, by performing pharmacokinetic evaluation in animal models

1.     To characterize the role of GAPDH and identify other M.tb Lactoferrin receptors

2.     To understand the trafficking of iron by this process

3.     To provide a structural basis for this interaction

4.     To identify key residues involved in the interaction of GAPDH -Lactoferrin

To develop multiple emulsion containing insulin and a permeation enhancer stabilized with secondary protein to improve gastrointestinal stability, permeability and therefore oral bioavailability of insulin

Development of tumor targeted siRNA complexed lipidic nano formulation

1.     Cloning, expression and purification of cytidine deaminase (CDA).

2.     CDA specific internalising RNA aptamer isolation using systemic evolution of ligands by exponential enrichment (SELEX).

3.     Functional validation of enriched CDA specific aptamer in differentially expressing cell lines.

4.     Synthesis of PLGA-PEG-COOH nanoparticle-aptamer conjugate containing modified nucleotides (5hmdC and 5fdC).

5.     Invitro and invivo evaluation of nanoparticle-aptamer conjugate for targeted delivery of 5hmdC and 5fdC and downstream effect on cancer proliferation.

1.     Synthesis of Mansouramycin D

2.     Structure Activity Relationship (SAR) study

3.     Anticancer study

4.     Identification of hits

5.     IP protection and patent filing

6.     Target identification and validation

7.     Pharmacokinetics profiling and identification of Lead