In silico identification and validation of phenolic lipids as potential inhibitor against bacterial and viral strains.

The recurrence of coronavirus disease and bacterial resistant strains has drawn attention to naturally occurring bioactive molecules that can demonstrate broad-spectrum efficacy against bacteria as well as viral strains. The drug-like abilities of naturally available "anacardic acids" (AA) and their derivatives against different bacterial and viral protein targets through in-silico tools were explored. Three viral protein targets [P DB: 6Y2E (SARS-CoV-2), 1AT3 (Herpes) and 2VSM (Nipah)] and four bacterial protein targets [P DB: 2VF5 (Escherichia coli), 2VEG (Streptococcus pneumoniae), 1JIJ (Staphylococcus aureus) and 1KZN (E. coli)] were selected to evaluate the activity of bioactive AA molecules. The potential ability to inhibit the progression of microbes has been discussed based on the structure, functionality and interaction ability of these molecules on the selected protein targets for multi-disease remediation. The number of interactions, full-fitness value and energy of the ligand-target system were determined from the docked structure in SwissDock and Autodock Vina. In order to compare the efficacy of these active derivatives to that of commonly used drugs against bacteria and viruses, a few of the selected molecules were subjected to 100 ns long MD simulations. It was found that the phenolic groups and alkyl chains of AA derivatives are more likely to bind with microbial targets, that could be responsible for the improved activity against these targets. The results suggest that the proposed AA derivatives have demonstrated potential to become active drug ingredients against microbial protein targets. Further, experimental investigations are essential for clinical verification of the drug-like abilities of AA derivatives.Communicated by Ramaswamy H. Sarma.

Mechanosynthesis of Stable Salt Hydrates of Allopurinol with Enhanced Dissolution, Diffusion, and Pharmacokinetics.

Allopurinol (ALO) is a medication that treats gout and kidney stones by lowering uric acid synthesis in the blood. The biopharmaceutics classification system (BCS) IV drug exhibits poor aqueous solubility, permeability, and bioavailability. To overcome the bottlenecks of ALO, salts with maleic acid (MLE) and oxalic acid (OXA) were synthesized using the solvent-assisted grinding method. The novel multicomponent solids were characterized by PXRD, DSC, TGA, FT-IR, and SEM images. The crystal structures of these salts with variable stoichiometry were obtained using Rietveld refinement from the high-resolution PXRD data. The proton from the dicarboxylic acid is transferred to the most basic pyrimidine "N" of ALO. The N-H···N hydrogen-bonded ALO homodimer is replaced by the N+-H···O- ionic interactions in ALO-OXA (2:1:0.4) and ALO-MLE (1:1:1) salt hydrates. The organic salts improved solubility and dissolution up to 5-fold and the diffusion permeability up to 12 times compared to the native drug in a luminal pH 6.8 phosphate buffer medium. The salt hydrates were exceptionally stable during storage at 30 ± 5 °C and 75 ± 5% relative humidity. Superior dissolution and diffusion permeability of the ALO-MLE salt resulted in improved pharmacokinetics (peak plasma concentration) that offers a promising solid dosage form with enhanced bioavailability and lower dosage formulation.

Insights into structural, spectroscopic, and hydrogen bonding interaction patterns of nicotinamide-oxalic acid (form I) salt by using experimental and theoretical approaches.

In the present work, nicotinamide-oxalic acid (NIC-OXA, form I) salt was crystallized by slow evaporation of an aqueous solution. To understand the molecular structure and spectroscopic properties of NIC after co-crystallization with OXA, experimental infrared (IR), Raman spectroscopic signatures, X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) techniques were used to characterize and validate the salt. The density functional theory (DFT) methodology was adopted to perform all theoretical calculations by using the B3LYP/6-311++G (d, p) functional/basis set. The experimental geometrical parameters were matched in good correlation with the theoretical parameters of the dimer than the monomer, due to the fact of covering the nearest hydrogen bonding interactions present in the crystal structure of the salt. The IR and Raman spectra of the dimer showed the red (downward) shifting and broadening of bands among (N15-H16), (N38-H39), and (C13=O14) bonds of NIC and (C26=O24), (C3=O1), and (C26=O25) groups of OXA, hence involved in the formation of NIC-OXA salt. The atoms in molecules (AIM) analysis revealed that (N8-H9···O24) is the strongest (conventional) intermolecular hydrogen bonding interaction in the dimer model of salt with the maximum value of interaction energy -12.1 kcal mol-1. Furthermore, the natural bond orbital (NBO) analysis of the Fock matrix showed that in the dimer model, the (N8-H9···O24) bond is responsible for the stabilization of the salt with an energy value of 13.44 kcal mol-1. The frontier molecular orbitals (FMOs) analysis showed that NIC-OXA (form I) salt is more reactive and less stable than NIC, as the energy gap of NIC-OXA (form I) salt is less than that of NIC. The global and local reactivity descriptor parameters were calculated for the monomer and dimer models of the salt. The electrophilic, nucleophilic, and neutral reactive sites of NIC, OXA, monomer, and dimer models of salt were visualized by plotting the molecular electrostatic potential (MESP) surface. The study provides valuable insights into combining both experimental and theoretical results that could define the physicochemical properties of molecules.

Thyroid Dysfunction and its Significance in Heart Failure.

INTRODUCTION: Studies show a high prevalence of thyroid dysfunction in heart failure patients that could have an impact on clinical course and outcome. MATERIALS: A total of 185 consecutive heart failure patients aged >18 years (mean age 58.4 years; 57.3% males) underwent demographic, clinical, hematological, biochemical and thyroid profile assessment. Euthyroidism was defined as TSH of 0.5 to 4.94 mIU/L with fT3 and fT4 in normal range, hypothyroidism as TSH of >4.94, and hyperthyroidism as TSH <0.5 mIU/L. Patients were followed up till discharge/outcome. Data was analyzed using SPSS 21.0 software. RESULT: Prevalence of thyroid disorders was 28.6% (6.5% hyper and 22.2% hypothyroid). No significant association of thyroid disorders was seen with age, sex, comorbidities and NT-proBNP levels (p > 0.05). Thyroid disorder was significantly associated with higher SBP, patients with NYHA 3/4, TSH, S. urea, S. creatinine and HDL levels and lower Hb, SGPT, TC and LDL levels (p < 0.05). Mean duration of hospital stay of patients with thyroid disorder was 3.74±0.92 days as compared to 3.45±0.86 days for those without thyroid disorder (p = 0.050). There were 12 (6.5%) mortalities. No significant association of mortality was seen with thyroid disorder (p = 0.711). CONCLUSION: There is high prevalence of thyroid disorders in heart failure patients which had a clinical impact too. Patients with thyroid disorder had higher NYHA and required longer hospitalization. Further studies to explore these relationships further are recommended. References Biondi B, Kahaly GJ. Cardiovascular involvement in patients with different causes of hyperthyroidism. Nat Rev Endocrinol 2010;6(8):431-443. Kuchulakanti PK, Bandaru S, Kuchulakanti A, et al. Association of subclinical hypothyroidism in heart failure: a study from South India. Br J Cardiol 2019;26:35. Jabbar A, Ingoe L, Thomas H, et al. Prevalence, predictors and outcomes of thyroid dysfunction in patients with acute myocardial infarction: the ThyrAMI-1 study. J Endocrinol Invest 2021;44(6):1209-1218.

Effect of donor parameters and cell separators on yield of apheresis platelet and their impact on corrected count increment in aplastic anemia patients.

BACKGROUND: The new cell separators make it simple to collect single donor platelets (SDP), although the platelet yield may vary depending on the cell separator used and donor-related clinical and laboratory variables. AIMS: This study aims to study the factors affecting SDP yield and corrected count increment (CCI). MATERIALS AND METHODS: This retrospective study was carried out at a tertiary care facility in northern India, over 4 years (May 2017-April 2020), data were retrieved and analyzed. STATISTICAL ANALYSIS: Categorical variables were presented as proportions, while continuous variables were presented as mean with standard deviation, P < 0.05 was considered significant. RESULTS: We found a positive correlation between predonation platelet count and yield (r = 0.243, P = 0.000). No such significant correlation was found with Hb concentration (r = 0.025, P = 0.720), age (r = 0.016, P = 0.820), sex (r = -0.038, P = 0.584), and weight (r = -0.025, P = 0.714). Maximum platelet yield and minimum time were seen with Trima. Only 39.3% (33/84) meet the 24 h CCI. The majority of patients did not meet the desired CCI could be due to the patients' clinical condition. On logistic regression, we found a significant association of 24 h CCI with product yield (odds ratio [OR] = 0.168, P = 0.015) and posttransfusion platelet count (OR = 0.454, P < 0.05). CONCLUSION: The only donor-related factor that influences yield is predonation platelet count, whereas 24 h CCI may depend on the clinical status of the patient and yield.

A case report on non-D HDFN: Highlighting the role of antibody screening in RhD positive antenatal women.

The widespread use of anti-D immunoglobulin has resulted in a relative increase in the importance of non-D alloimmunization as a cause of hemolytic disease of the fetus and newborn (HDFN). Non-D alloantibodies that are capable of causing severe HDFN include anti-K, anti-E, and anti-c. Anti-c is clinically the most important Rh system antibody after anti-D. Here, we report three cases of neonates presenting with anemia and hyperbilirubinemia with strongly positive direct antiglobulin test who required phototherapy and neonatal exchange transfusion due to non-D antibody in RhD positive antenatal women. Anti-c was common in all the three cases while two cases have one additional non-D antibody. Due to faulty practices, antenatal antibody screening was not done for any case considering the mother's RhD positive status. Hence, antenatal antibody screening should be performed routinely, in all RhD positive pregnant women to reduce the delay in diagnosis and the management of HDFN occurring due to non-D antibodies.

Experimental and Quantum Chemical Studies of Nicotinamide-Oxalic Acid Salt: Hydrogen Bonding, AIM and NBO Analysis.

The computational modeling supported with experimental results can explain the overall structural packing by predicting the hydrogen bond interactions present in any cocrystals (active pharmaceutical ingredients + coformer) as well as salts. In this context, the hydrogen bonding synthons, physiochemical properties (chemical reactivity and stability), and drug-likeliness behavior of proposed nicotinamide-oxalic acid (NIC-OXA) salt have been reported by using vibrational spectroscopic signatures (IR and Raman spectra) and quantum chemical calculations. The NIC-OXA salt was prepared by reactive crystallization method. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) techniques were used for the characterization and validation of NIC-OXA salt. The spectroscopic signatures revealed that (N7-H8)/(N23-H24) of the pyridine ring of NIC, (C═O), and (C-O) groups of OXA were forming the intermolecular hydrogen bonding (N-H⋯O-C), (C-H⋯O═C), and (N-H⋯O═C), respectively, in NIC-OXA salt. Additionally, the quantum theory of atoms in molecules (QTAIM) showed that (C10-H22⋯O1) and (C26-H38⋯O4) are two unconventional hydrogen bonds present in NIC-OXA salt. Also, the natural bond orbital analysis was performed to find the charge transfer interactions and revealed the strongest hydrogen bonds (N7-H8⋯O5)/(N23-H24⋯O2) in NIC-OXA salt. The frontier molecular orbital (FMO) analysis suggested more reactivity and less stability of NIC-OXA salt in comparison to NIC-CA cocrystal and NIC. The global and local reactivity descriptors calculated and predicted that NIC-OXA salt is softer than NIC-CA cocrystal and NIC. From MESP of NIC-OXA salt, it is clear that electrophilic (N7-H8)/(N23-H24), (C6═O4)/(C3═O1) and nucleophilic (C10-H22)/(C26-H38), (C6-O5)/(C3-O2) reactive groups in NIC and OXA, respectively, neutralize after the formation of NIC-OXA salt, confirming the presence of hydrogen bonding interactions (N7-H8⋯O5-C6) and (N23-H24⋯O2-C3). Lipinski's rule was applied to check the activeness of salt as an orally active form. The results shed light on several features of NIC-OXA salt that can further lead to the improvement in the physicochemical properties of NIC.

Evaluation of efficacy of Valsalva for attenuating needle puncture pain in first time nonremunerated voluntary plateletpheresis donors: A prospective, randomized controlled trial.

BACKGROUND: Plateletpheresis is generally safe but may have adverse reactions. Adverse reactions can negatively influence donor recruitment and retention. Valsalva is a proven method of attenuating pain caused by venipuncture. AIMS: The aim was to evaluate the efficacy of the Valsalva maneuver on the attenuation of needle pain and donor anxiety. SETTINGS AND DESIGN: This prospective randomized controlled trial was conducted between November 2015 and April 2016 at the Department of Transfusion Medicine. SUBJECTS AND METHODS: One-hundred and sixty consecutive donors were grouped into control group (C) and Valsalva group (V) each of sample size 80. The Valsalva group performed a Valsalva maneuver and control did nothing before the venipuncture. Anxiety and pain were scored using a 10 cm visual analog scale (VAS). Severity was graded as VAS = 0 defines no pain and anxiety, VAS = 1-3 as mild pain and anxiety, VAS = 4-6 as moderate pain and anxiety, VAS = 7-9 as severe pain and anxiety, whereas VAS = 10 denotes extreme pain and anxiety. STATISTICAL ANALYSIS: Statistical Package for Social Sciences, version 23 was used for analysis. Independent samples t-test/Mann-Whitney U-test was used to compare between treatment and control group, whereas the Wilcoxon signed-rank test was used to test the difference between pre- and postobservations. RESULTS: In the Valsalva group, post-Valsalva anxiety levels were significantly reduced to (1 [0-2]) from their pre-Valsalva values of (2 [0-3]); (P < 0.001). Pain was significantly lower (2[1-2]) in Valsalva group compared to control (4[2-5]); (P < 0.001). CONCLUSIONS: Valsalva reduced both severity of venipuncture pain and anxiety. Valsalva can be performed by donors as it is an easy, painless, and nonpharmacological method of pain and anxiety attenuation.

Molecular Structure, Spectral Investigations, Hydrogen Bonding Interactions and Reactivity-Property Relationship of Caffeine-Citric Acid Cocrystal by Experimental and DFT Approach.

The pharmaceutical cocrystal of caffeine-citric acid (CAF-CA, Form II) has been studied to explore the presence of hydrogen bonding interactions and structure-reactivity-property relationship between the two constituents CAF and Citric acid. The cocrystal was prepared by slurry crystallization. Powder X-ray diffraction (PXRD) analysis was done to characterize CAF-CA cocrystal. Also, differential scanning calorimetry (DSC) confirmed the existence of CAF-CA cocrystal. The vibrational spectroscopic (FT-IR and FT-Raman) signatures and quantum chemical approach have been used as a strategy to get insights into structural and spectral features of CAF-CA cocrystal. There was a good correlation among the experimental and theoretical results of dimer of cocrystal, as this model is capable of covering all nearest possible interactions present in the crystal structure of cocrystal. The spectroscopic results confirmed that (O33-H34) mode forms an intramolecular (C25 = O28∙∙∙H34-O33), while (O26-H27) (O39-H40) and (O43-H44) groups form intermolecular hydrogen bonding (O26-H27∙∙∙N24-C22, O39-H40∙∙∙O52 = C51 and O43-H44∙∙∙O86 = C83) in cocrystal due to red shifting and increment in bond length. The quantum theory of atoms in molecules (QTAIM) analysis revealed (O88-H89∙∙∙O41) as strongest intermolecular hydrogen bonding interaction with interaction energy -12.4247 kcal mol-1 in CAF-CA cocrystal. The natural bond orbital analysis of the second-order theory of the Fock matrix highlighted the presence of strong interactions (N∙∙∙H and O∙∙∙H) in cocrystal. The HOMO-LUMO energy gap value shows that the CAF-CA cocrystal is more reactive, less stable and softer than CAF active pharmaceutical ingredients. The electrophilic and nucleophilic reactivities of atomic sites involved in intermolecular hydrogen bond interactions in cocrystal have been demonstrated by mapping electron density isosurfaces over electrostatic potential i.e. plotting molecular electrostatic potential (MESP) map. The molar refractivity value of cocrystal lies within the set range by Lipinski and hence it may be used as orally active form. The results show that the physicochemical properties of CAF-CA cocrystal are enhanced in comparison to CAF (API).

Abacavir-based Regimen for HIV-infected Children and Adolescents.

We studied 48 children receiving abacavir-based HAART regimen, over a period of one-year for side effects and failure rates. None of the children developed hypersensitivity reaction. The CD4 count significantly improved from the time of enrolment till 12 months of therapy while the failure rate was 14.5%.

Study of molecular structure and hydrogen bond interactions in dipfluzine-benzoic acid (DIP-BEN) cocrystal using spectroscopic and quantum chemical method.

The purpose of this article is to predict the molecular structure of the cocrystal of dipfluzine-benzoic acid (DIP-BEN) through computational approach (DFT calculations) and validate it using vibrational spectroscopic studies. The molecular structure of the DIP-BEN cocrystal has been predicted by forming models on the basis of the active sites available to form H-bonds between dipfluzine (DIP) and benzoic acid (BEN). Conformational study has been performed and potential energy surface scans are plotted around the flexible bonds of the cocrystal molecule and three stable conformers have been obtained. Quantum theory of atoms in molecules (QTAIM) explains that all the interactions are medium and partially covalent in nature. Natural bond orbital analysis of the second order perturbation theory of the Fock matrix suggests that interactions LP (2) O2 → σ*(O74H75) and LP (2) F1 → σ* (O89H90) are responsible for the stabilization of the molecule. The HOMO and LUMO energies and electronic charge transfer (ECT) confirms that charge flows from BEN to DIP. Global reactivity descriptor parameters suggest that DIP-BEN cocrystal is softer, thus more reactive in comparison to DIP. Local reactivity descriptor parameter is used to predict reactive sites of the cocrystal. The experimental and theoretical results support the formation of cocrystal through strong hydrogen bond (O89H90⋯F1 and O74H75⋯O2) interactions present in cocrystal.

Spectroscopic and molecular structure (monomeric and dimeric model) investigation of Febuxostat: A combined experimental and theoretical study.

Febuxostat (FXT) is a urate-lowering drug and xanthine oxidase inhibitor which is used for the treatment of hyperuricemia and gout caused by increased levels of uric acid in the blood (hyperuricemia). The present study aims to provide deeper knowledge of the structural, vibrational spectroscopic and physiochemical properties of FXT based on monomeric and dimeric model with the aid of combination of experimental and computational methods. The conformational analysis of form Q has been done to predict the possible structure of unknown form A. Vibrational spectra of form A and Q has been compared to get an idea of hydrogen bonding interactions of form A. A computational study of FXT has been executed at different level (B3LYP, M06-2X, WB97XD) of theory and 6-31 G (d, p) basis set for dimeric model to elucidate the nature of intermolecular hydrogen bond. The red shift observed in the stretching modes of OH, CO groups and blue shift in stretching mode of CN group in experimental as well as in theoretical spectra explains the involvement of these groups in intermolecular hydrogen bonding. NBO analysis shows that change in electron density (ED) in the lone pair orbital to σ* antibonding orbital (LP1 (N39) → σ* (O3-H38)) with maximum value of E(2) energy confirms the presence of hydrogen bond (N39⋯H38-O3) leading to dimer formation. Study of topological parameters was executed for dimer using Bader's atoms in molecules (AIM) theory predicting the partially covalent nature of hydrogen bonds present in the molecule. The study of molecular electrostatic potential surface (MEPS) map ascertains that the CO, CN group are prone to electrophilic attack and OH group is active towards nucleophilic attack. The lower energy band gap and higher value of softness of dimeric model of FXT indicates its more reactivity, polarisability than monomeric model. The local reactivity descriptors predict the order of reactive sites towards electrophilic, nucleophilic and radical attack. An investigation made to determine the ligand protein interaction of FXT through docking with different molecular targets reveals the inhibitive as well as antibacterial nature of FXT.

A combined experimental (IR, Raman and UV-Vis) and quantum chemical study of canadine.

Plant based natural products cover a major sector of the medicinal field, as such focus on plant research has been increased all over the world. As an attempt to aid that research, we have performed structural and spectroscopic analysis of a natural product, an alkaloid: canadine. Both ab initio Hartree-Fock (HF) and density functional theory (DFT) employing B3LYP using 6-311++G(d,p) basis set were used for the calculations. The calculated vibrational frequencies were scaled and compared with the experimental infrared and Raman spectra. The complete vibrational assignments were made using potential energy distribution. The structure-activity relation has also been interpreted by mapping electrostatic potential surface and evaluating the reactivity descriptors, which are valuable information for quality control of medicines and drug-receptor interactions. Natural bond orbital analysis has also been performed to understand the stability and hyperconjugative interactions of the molecule. Furthermore, UV-Vis spectra have been recorded in an ethanol solvent (EtOH) and the electronic property has been analyzed employing TD-DFT for both gaseous and solvent phase. The HOMO and LUMO calculation with their energy gap show that charge transfer occurs within the molecule. Additionally, the nonlinear optical properties of the title compound have been interpreted that predicts it's the best candidate for the NLO materials.

Metabolic Derangement in Acute and Chronic Liver Disorders.

AIMS: This study aims to assess glycemic and lipid derangement in acute and chronic liver disorders. MATERIALS AND METHODS: A cross-sectional study was conducted on 104 patients diagnosed with acute or chronic liver disorder. Acute liver disease (ALD) patients were 40 and chronic liver disease (CLD) patients were 64. RESULTS: The mean value of fasting plasma glucose (FPG) in patients with ALD was 91.8 ± 5.4 mg/dl and in CLD was 115.7 ± 17.9 mg/dl, the difference was significant. The mean value of A1c was 4.3 ± 0.6 in ALD and 6.1 ± 0.8 in CLD, the difference was significant. In patients with CLD mean cholesterol was higher 177.4 ± 28.8 mg/dl when compared to ALD 140 ± 35.1 mg/dl, but the difference was not significant. ALD patients' high-density lipoprotein (HDL) was 50.4 ± 5.1 mg/dl, and in CLD patients, HDL was 44.4 ± 6.1 mg/dl. In CLD mean triglyceride (T) was 148.9 ± 6.4 mg/dl while in ALD T was 134.8 ± 14.2 mg/dl, the difference was significant. CONCLUSIONS: CLD is associated with glycemic derangement demonstrated by deranged FPG and A1c. In patients of ALD, no metabolic derangement was observed.

Double Dose Versus Standard Dose Hepatitis B Vaccine in HIV-infected Children: A Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of double dose (20 µg) with standard dose (10 µg) of hepatitis B vaccine in HIV-infected children. METHODS: Unvaccinated HIV-infected children were randomized to receive 3 doses of double dose (N=27) or standard dose (N=28) of recombinant Hepatitis B vaccine. Anti-HBs antibody titres were measured 3 mo after the last dose. An antibody titre ≥10 mIU/mL 12 weaks after the third dose was considered as serporotection. RESULTS: Seroprotection was achieved by 17 (60.7%) children in standard dose group against 20 (74%) in the double dose group [RR (95%CI) 0.8 (0.17-1.7); P=0.29]. CD4 count < 500 cells/mm3 was significantly associated with lower rates of seroprotection. CONCLUSION: Double dose of hepatitis B vaccine does not seem to provide any advantage when compared to standard dose in HIV-infected children.

Spectroscopic (far or terahertz, mid-infrared and Raman) investigation, thermal analysis and biological activity of piplartine.

Research in the field of medicinal plants including Piper species like long pepper (Piper longum L.- Piperaceae) is increasing all over the world due to its use in traditional and Ayurvedic medicine. Piplartine (piperlongumine, 5,6-dihydro-1-[(2E)-1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)-pyridinone), a biologically active alkaloid/amide was isolated from the phytochemical investigations of Piper species, as long pepper. This alkaloid has cytotoxic, anti-fungal, anti-diabetic, anti-platelet aggregation, anti-tumoral, anxiolytic, anti-depressant, anti-leishmanial, and genotoxic activities, but, its anticancer property is the most promising and has been widely explored. The main purpose of the work is to present a solid state characterization of PPTN using thermal analysis and vibrational spectroscopy. Quantum mechanical calculations based on the density functional theory was also applied to investigate the molecular conformation and vibrational spectrum, which was compared with experimental results obtained by Raman scattering, far (terahertz) and mid-infrared adsorption spectroscopy. NBO analysis has been performed which predict that most intensive interactions in PPTN are the hyperconjugative interactions between n(1) N6 and π*(O1C7) having delocalization energy of 50.53kcal/mol, Topological parameters have been analyzed using 'AIM' analysis which governs the three bond critical points (BCPs), one di-hydrogen, and four ring critical points (RCPs). MEP surface has been plotted which forecast that the most negative region is associated with the electronegative oxygen atoms (sites for nucleophilic activity). Theoretically, to confirm that the title compound has anti-cancer, anti-diabetic and anti-platelet aggregation activities, it was analyzed by molecular docking interactions with the corresponding target receptors. The obtained values of H-bonding parameters and binding affinity prove that its anti-cancer activity is the more prominent than the other properties.

Characterization and intramolecular bonding patterns of busulfan: Experimental and quantum chemical approach.

The investigations of structural conformers, molecular interactions and vibrational characterization of pharmaceutical drug are helpful to understand their behaviour. In the present work, the 2D potential energy surface (PES) scan has been performed on the dihedral angles C6O4S1C5 and C25S22O19C16 to find the stable conformers of busulfan. In order to show the effects of long range interactions, the structures on the global minima of PES scan have been further optimized by B3LYP/6-311++G(d,p) method with and without empirical dispersion functional in Gaussian 09W package. The presence of n→σ* and σ→σ* interactions which lead to stability of the molecule have been predicted by natural bond orbital analysis. The strong and weak hydrogen bonds between the functional groups of busulfan were analyzed using quantum topological atoms in molecules analysis. In order to study the long-range forces, such as van der Waals interactions, steric effect in busulfan, the reduced density gradient as well as isosurface defining these interactions has been plotted using Multiwfn software. The spectroscopic characterization on the solid phase of busulfan has been studied by experimental FT-IR and FT-Raman spectra. From the 13C and 1H NMR spectra, the chemical shifts of individual C and H atoms of busulfan have been predicted. The maximum absorption wavelengths corresponding to the electronic transitions between the highest occupied molecular orbital and the lowest unoccupied molecular orbital of busulfan have been found by UV-vis spectrum.

Prevalence of hypothyroidism in diabetic kidney disease and effect of thyroid hormone replacement on estimate glomerular filtration rate.

AIMS: To determine the prevalence of subclinical and overt hypothyroidism in diabetic kidney disease (DKD) and effect of thyroid hormone replacement on progression of DKD. MATERIALS AND METHODS: A prospective cohort study on 41 adult DKD patients who were screened for hypothyroidism. Hypothyroid DKD patients were started on levothyroxine replacement and were reviewed after 3 and 6 months. RESULTS: Of the total population, 14 (34.1%) cases were hypothyroid, among whom 12 (29.3%) cases were subclinical, and 2 (4.8%) were overt hypothyroidism. Prevalence of hypothyroidism and mean thyroid stimulating hormone levels increased with increasing severity of DKD. There were 2 (14.3%) hypothyroid cases in stage 3b, 4 (28.5%) cases in stage 4, and 8 (57.2%) in stage 5 DKD. The mean estimate glomerular filtration rate (ml/min/1.73 m2) at baseline was 13.6 ± 13.3 which increased to 16.4 ± 14.5 and 21.2 ± 15.3 after 3 and 6 months of thyroid hormone replacement therapy (THRT), respectively (P < 0.001). CONCLUSIONS: Hypothyroidism is commonly associated with DKD. Prevalence of hypothyroidism increased with declining renal function. THRT significantly improved renal function in DKD patients with hypothyroidism after 3 and 6 months of therapy.