C.M. Anuradha

Publications (13) View all

• Article: Synthesis and evaluation of resveratrol derivatives as new chemical entities for cancer.

  Chaitanya Mulakayala, B Babajan, P Madhusudana, C M Anuradha, Raja Mohan Rao, Ravi Prakash Nune, Sunil Kumar Manna, Naveen Mulakayala, Chitta Suresh Kumar
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  ABSTRACT: Resveratrol has been shown to be active in inhibiting multistage carcinogenesis. The potential use of resveratrol in cancer chemoprevention or chemotherapy settings has been hindered by its short half-life and low bioavailability. Considering the above remarks, using resveratrol as a prototype, we have synthesized two derivatives of resveratrol. Their activity was evaluated using in vitro and in silico analysis. Biological evaluation of resveratrol analogues on U937 cells had shown that two synthesized analogues of resveratrol had higher rates of inhibition than the parental molecule at 10μM concentration. EMSA conducted for NF-kB revealed that these molecules significantly interfered in the DNA binding ability of NF-kB. It was found that these molecules suppressed the expression of TNFα, TNFR, IL-8, actin and activated the expression of FasL, FasR genes. To understand possible molecular mechanism of the action we performed docking and dynamic studies, using NF-kB as a receptor. Results showed that resveratrol, RA1 and RA2 interacted with the residues involved in DNA binding. Resveratrol analogues by interacting NF-kB might have prevented its translocation and also by interacting with the residues involved in DNA binding might have prevented the binding of NF-kB to DNA. This may be the reason for suppression of NF-kB binding to DNA.
  Journal of molecular graphics & modelling 02/2013; 41C:43-54. · 2.17 Impact Factor
• Article: Molecular characterization of Mtb-OMP decarboxylase by modeling, docking and dynamic studies.

  P Madhusudana, B Babajan, M Chaitanya, C M Anuradha, C Shobharani, Rajasekar Chikati, Chitta Suresh Kumar, K R S Sambasiva Rao, Sudhakar Poda
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  ABSTRACT: Tuberculosis (TB), the second most deadly disease in the world is caused by Mycobacterium tuberculosis (Mtb). In the present work a unique enzyme of Mtb orotidine 5' monophosphate decarboxylase (Mtb-OMP Decase) is selected as drug target due to its indispensible role in biosynthesis of pyrimidines. The present work is focused on understanding the structural and functional aspects of Mtb-OMP Decase at molecular level. Due to absence of crystal structure, the 3D structure of Mtb-OMP Decase was predicted by MODELLER9V7 using a known structural template 3L52. Energy minimization and refinement of the developed 3D model was carried out with Gromacs 3.2.1 and the optimized homology model was validated by PROCHECK,WHAT-IF and PROSA2003. Further, the surface active site amino acids were quantified by WHAT-IF pocket. The exact binding interactions of the ligands, 6-idiouridine 5' monophosphate and its designed analogues with the receptor Mtb-OMP Decase were predicted by docking analysis with AUTODOCK 4.0. This would be helpful in understanding the blockade mechanism of OMP Decase and provide a candidate lead for the discovery of Mtb-OMP Decase inhibitors, which may bring insights into outcome new therapy to treat drug resistant Mtb.
  Interdisciplinary Sciences Computational Life Sciences 06/2012; 4(2):142-52.
• Article: Probing ligand binding modes of Mycobacterium tuberculosis MurC ligase by molecular modeling, dynamics simulation and docking

  C. M. Anuradha, Chaitanya Mulakayala, Banaganapalli Babajan, M. Naveen, Chikati Rajasekhar, Chitta Suresh Kumar
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  ABSTRACT: Multi drug resistance capacity for Mycobacterium tuberculosis (MDR-Mtb) demands the profound need for developing new anti-tuberculosis drugs. The present work is on Mtb-MurC ligase, which is an enzyme involved in biosynthesis of peptidoglycan, a component of Mtb cell wall. In this paper the 3-D structure of Mtb-MurC has been constructed using the templates 1GQQ and 1P31. Structural refinement and energy minimization of the predicted Mtb-MurC ligase model has been carried out by molecular dynamics. The streochemical check failures in the energy minimized model have been evaluated through Procheck, Whatif ProSA, and Verify 3D. Further torsion angles for the side chains of amino acid residues of the developed model were determined using Predictor. Docking analysis of Mtb-MurC model with ligands and natural substrates enabled us to identify specific residues viz. Gly125, Lys126, Arg331, and Arg332, within the Mtb-MurC binding pocket to play an important role in ligand and substrate binding affinity and selectivity. The availability of Mtb-MurC ligase built model, together with insights gained from docking analysis will promote the rational design of potent and selective Mtb-MurC ligase inhibitors as antituberculosis therapeutics. KeywordsDocking-Gromacs-Modellar9v.3-Mtb-MurC ligase-NAM-RMSD-Tuberculosis
  Journal of Molecular Modeling 04/2012; 16(1):77-85. · 1.80 Impact Factor
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  Article: Nutrigenetic Traits Analysis for the Identification of Nutritionally Efficient Silkworm Germplasm Breeds

  Ramesha C, Anuradha C.M, Lakshmi H, S. Sugnana Kumari, Seshagiri S.V, Goel A.K, C. Suresh Kumar
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  ABSTRACT: In order to amalgamate the effects of nutrition and its efficiency on genetic traits expression in silkworm germplasm breeds by serial analysis on nutrigenetic traits and utilized as biomarker with an aim to identify nutritionally efficient silkworm germplasm breeds. In the present study, six bivoltine silkworm breeds were subjected for investigation on ingestion, digestion and utilization of dry food matter in single silkworm larva and its sharing on economically important stages larva, cocoon and shell weight in 5th stage. It was resolved that low consumption with high conversion efficiency of food ingested in silkworm breeds on nineteen nutrigenetic traits analyzed by standard gravimetric method with the aid of INDOSTAT software to understand the nutrigenomic divergence among the silkworm germplasm breeds against different seasons. Results indicated that higher conversion efficiency was observed in most of the new silkworm breeds for Efficiency of Conversion of Ingesta (ECI) to cocoon and shell than control (APS₈) as leaf - cocoon and leaf-shell conversion are the ultimate indices in nutrigenomic analysis. It also demonstrated that relatively smaller amount of Consumption Index (CI), respiration, Metabolic Rate (MR) with superior Relative Growth Rate (RGR) and in relation to quantum of food ingesta and digesta requisite per gram of cocoon and shell found less than the control. This concluded that nutrigenetic traits directly associated to the quantum of food ingesta and digesta g^-1of cocoon and shell and such nutrigenetic study pragmatically utilized as biomarkers in order to advocate sturdily the following breeds viz., RBD₁, RBD₄ (peanut type cocoon), RBO₂, RBO₃ (oval type cocoon) were chosen as highly nutritionally efficient bivoltine silkworm germplasm breeds.
  Biotechnology. 01/2010;
• Article: Comprehensive structural and functional characterization of Mycobacterium tuberculosis UDP-NAG enolpyruvyl transferase (Mtb-MurA) and prediction of its accurate binding affinities with inhibitors.

  B Babajan, M Chaitanya, C Rajsekhar, D Gowsia, P Madhusudhana, M Naveen, Suresh Kumar Chitta, C M Anuradha
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  ABSTRACT: Tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death in the world. One third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of TB. The bacterial enzyme MurA catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first committed step of bacterial cell wall biosynthesis. In this work, 3D structure model of Mtb-MurA enzyme has been developed for the first time by homology modeling and molecular dynamics simulation techniques. Multiple sequence alignment and 3D structure model provided the putative substrate binding pocket of Mtb-MurA with respect to E. coli MurA. This analysis was helpful in identifying the binding sites and molecular function of the MurA homologue. Molecular docking study was performed on this 3D structure model, using different classes of inhibitors like fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic acid derivatives T6361, T6362 and the results showed that the 5-sulfonoxyanthranilic acid derivatives showed the best interaction compared to other inhibitors. We also designed new efficient analogs of T6361 and T6362 which showed even better interaction with Mtb-MurA than the parental 5-sulfonoxy-anthranilic acid derivatives. Further the comparative molecular electrostatic potential and cavity depth analysis of Mtb-MurA suggested several important differences in its substrate and inhibitor binding pocket. Such differences could be exploited in the future for designing a more specific inhibitor for Mtb-MurA enzyme.
  Interdisciplinary Sciences Computational Life Sciences 09/2011; 3(3):204-16.