Investigation of miscibiliy and physicochemical properties of synthetic polypeptide with collagen blends and their wound healing characteristics.

A suitable condition is needed to foster a rapid recovery of wounds, which is a dynamic and intricate process. The development and characterization of mats of plastic-like peptide polymer (PLP) with collagen for wound healing applications are reported in this work. Viscosity parameters such as the Huggins coefficient [KH], the intrinsic viscosity [η], α by Sun, ∆[η]m by Garcia ∆B and µ suggested by Chee, ∆K, and ß advocated by Jiang and Han, recommend the miscibility of the polypeptide in solution phase. Fourier transform infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and X-ray diffraction (XRD) methods in a solid phase. Thermal characteristics using a differential scanning calorimeter (DSC) and thermogravimetric analysis (TGA) showed higher stability for the blends than the pure polymers. The collagen and PLP blends showed exceptional in vitro cytocompatibility, and the in vivo wound-healing studies on the Sprague-Dawley rats demonstrated faster wound healing within two weeks compared to the cotton gauze-treated injuries. Therefore, these membranes can be a possible alternative for treating skin injuries.

Multitarget-directed therapeutics: (Urea/thiourea)2 derivatives of diverse heterocyclic-Lys conjugates.

The synthesis of a new small library of molecules containing bis-urea/thiourea pendants in lysine conjugated to three different heterocycles is described. The heterocycles used in this study have benzisoxazole/piperazine/piperidine units. After a detailed antimicrobial, antioxidant, and anti-inflammatory evaluation, it was found that the most active compounds are 10, 11, 14, 15, 18, 19 and 10, 11, 19 and 8, 9, 12, 13, 16, 17, respectively. Further, it was observed that the presence of all three entities, that is, urea/thiourea, the substituent (OMe/F), as well as the heterocycle, is highly essential for exerting potent activity. Among the heterocycles, the presence of isoxazole seems to be highly beneficial for exerting good potency. In continuation, docking studies have revealed extraordinary binding efficiency for some of the active compounds. Given their potent biological results and docking score, some of the title compounds could be potential drug candidates for microbial-related diseases and provide a basis for future research into the development of molecules possessing multitask ability.

Amino acids conjugated quinazolinone-Schiff's bases as potential antimicrobial agents: Synthesis, SAR and molecular docking studies.

A series of amino acids conjugated quinazolinone-Schiff's bases were synthesized and characterized by analytical and spectroscopic methods. All the synthesized analogues (8-43) and the intermediates (1-7) were screened for their in vitro antibacterial and antifungal activities. In antimicrobial activity, compounds 12-16, 21-25, 30-34 and 39-43 showed excellent antibacterial activity which is better than the antibacterial standard Streptomycin. Compounds 15, 23-25, 30-34, 36 and 38-43 showed excellent antifungal activities which is more active than the reference antifungal drug Bavistin. Further, to understand the correlation of biological activity with that of drug-receptor interaction, molecular docking was performed on active site ofglucosamine-6-Phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) which showed good binding profile. Molecular docking studies and Preliminary structure-activity (SAR) relationship revealed that the tryptophan and phenylalanine conjugated quinazolinones with electron donating groups (OH and OCH3) were found to be excellent antimicrobial activities which is better than the glycine and alanine conjugated derivatives. This may be explained by the contribution of aromaticity and hydrophobicity of amino acids. Among the series, compounds 41 and 43 showed the highest docking scores for antimicrobial activity. The conjugation plays a major role in improving the biological activities of those compounds.

Anticancer and DNA binding studies of potential amino acids based quinazolinone analogs: Synthesis, SAR and molecular docking.

A novel series of amino acids conjugated quinazolinone-Schiff's bases were synthesized and screened for their in vitro anticancer activity and validated by molecular docking and DNA binding studies. In the present investigations, compounds 32, 33, 34, 41, 42 and 43 showed most potent anticancer activity against tested cancer cell lines and DNA binding study using methyl green comparing to doxorubicin and ethidium bromide as a positive control respectively. The structure-activity relationship (SAR) revealed that the tryptophan and phenylalanine derived electron donating groups (OH and OCH3) favored DNA binding studies and anticancer activity whereas; electron withdrawing groups (Cl, NO2, and F) showed least anticancer activity. The molecular docking study, binding interactions of the most active compounds 33, 34, 42 and 43 stacked with A-T rich regions of the DNA minor groove by surface binding interactions were confirmed.

Miscibility studies of plastic-mimetic polypeptide with hydroxypropylmethylcellulose blends and generation of non-woven fabrics.

In the current investigation, the results of viscometric measurements, thermal property, SEM, XRD and FTIR of the polymer blends containing synthetic plastic-based polypeptide (PLP) with hydroxypropylmethylcellulose (HPMC) on miscibility is discussed. Various interaction parameters; KH, Δ[η]m, ΔB, µ, α, ß and ΔK indicated the miscibility of polypeptide/HPMC up to 40% of the PLP in the blend at room temperature. The calorimetric results a single glass transition event for miscible systems. Further, the results were aligned with the scanning electron microscope and XRD analysis. Details concerning the nature of interactions in these systems and how they are influenced by the peptide proportion in the blends are discussed. The thermo gravimetric analysis manifested the improved thermal stability of the blends than their individual polymers. Additionally, the blend solutions were fabricated into non-woven fabrics with electrospinning technique, which may be a good candidate for pharmaceutical and biomedical applications.

Imidazolo and tryptophan-imidazolo hybrid derived ureas/thioureas as potent bioactive agents - SAR and molecular modelling studies.

Herein, we used an imidazole derivative (IMD) which showed promising antibacterial, antifungal and antioxidant properties in our earlier investigation. Prompted by this, we converted IMD to hydrazide (IMH) by hydrazinolysis which was derivatized to various ureas (3-7) and thioureas (8-12). On the other hand, IMH was conjugated to Boc-Trp-OH as it has been shown in the past that hybridization of two molecules produced promising biologically active compounds. Boc of the conjugate was removed and further converted into several urea (14-18) and thiourea (19-23) derivatives. All the title compounds so also the starting materials and intermediates were assessed for potential biological applications. The results showed that compounds 3, 4, 8, 9, 14, 15, 19 and 20 were excellent antioxidants as revealed by DPPH, DMPD and ABTS assays. Further, certain analogues like 5-7, 10-12, 16-18 and 21-23 were found to be potent antimicrobials against pathogenic bacteria and fungi whereas good anti-inflammatory activity was obtained for molecules 5-7, 10-12, 16-18 and 21-23. All together, derivatives of the conjugates have shown superior activity over non-conjugated compounds and the former have exhibited potent activity against standard drugs in all the assays. In a quest to understand the binding interactions of the compounds with active site of tyrosine kinase (PDB ID: 2HCK), glucosamine-6-phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) and cyclooxygenase-2 (PDB ID: 1CX2) enzymes, the correlation studies were conducted using molecular modelling which showed good receptor binding interactions with several amino acids of the enzymes. Overall, the current investigation may be considered for the discovery of lead compound(s) for treating multiple disorder conditions using singular molecular entity.

A correlation study of biological activity and molecular docking of Asp and Glu linked bis-hydrazones of quinazolinones.

The present investigation involves the synthesis and spectroscopic and biological activity studies of the bis-hydrazones of quinazolinones derived from aspartic acid and glutamic acid. The antioxidant activities of the compounds were evaluated using DPPH, DMPD and ABTS radical scavenging assays whose results revealed that the IC50 of compounds 6, 7, 11, 12, 20, 21, 25 and 26 was lower than those of the standard references. The anti-inflammatory activity was evaluated with a haemolysis assay using a human blood erythrocytes suspension and the results demonstrated that compounds 8, 9, 13, 14, 22, 23, 27 and 28 were excellent anti-inflammatory agents. In addition, the antibacterial and antifungal activities against various clinical pathogens of human origin revealed that compounds 7, 9, 12, 14, 21, 23, 26 and 28 possessed potent antimicrobial properties. Furthermore, to understand the correlation between biological activity and drug-receptor interaction, molecular docking was performed on the active sites of tyrosine kinase (PDB ID: 2HCK), cyclooxygenase-2 (PDB ID: 1CX2) and glucosamine-6-phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) which showed good binding profiles with the targets that can potentially hold the title compounds. The correlation study revealed that compounds containing EDGs (-OH, -OCH3) were excellent antioxidants, compounds with EWGs (-Cl, -NO2) exhibited good anti-inflammatory activity and compounds bearing -OH and -NO2 groups were very good antimicrobials.

Amino acids/peptides conjugated heterocycles: A tool for the recent development of novel therapeutic agents.

Amino acids/peptide conjugated heterocycles represent an important class of therapeutical agents. Biologically active heterocycles are conjugated with amino acids or peptides to increase the drug resistance. Furthermore, the amino acid/peptide based drugs have low toxicity, ample bioavailability and permeability, modest potency and good metabolic and pharmacokinetic properties. Synthetic amino acid/peptides based heterocyclic conjugates constitute a promising choice for the development of new, less toxic and safer conventional pharmaceutical drugs in the near future. In this review, we discuss and highlight the recent findings of the structural features that encourage biological applications of amino acid/peptides based conjugates.

Design and synthesis of amino acids-conjugated heterocycle derived ureas/thioureas as potent inhibitors of protein glycation.

Protein glycation is believed to play an important role in the development of long-term disorders associated with diabetic complications. In view of the wide occurrence of advanced glycation end products (AGE's) and the oxidative stress derived from them in a variety of diabetic complications, it would be of great interest to identify and develop AGE inhibitors. In this study, synthesis and in vitro antiglycation activity of a small library of forty urea/thiourea derivatives of Phe/Tyr/Glu/Lys-benzisoxazole hybrids are reported. Structures of the compounds were confirmed by IR, NMR, mass spectrometry, and elemental analysis. Most of the title compounds exhibited promising activity. Best antiglycation activity was found for Tyr analogue with methoxy group as a substituent particularly at the para position with IC50 value of 1.9 microM against the positive control, Rutin, with IC50 = 41.9 microM. Thus, the title compounds represent novel class of potent antiglycating agents.

tert-Butyl 1,5-bis(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)-1,5-dioxopentan-2-ylcarbamate urea/thiourea derivatives as potent H+/K(+)-ATPase inhibitors.

Amino acids are known to possess variable efficacy against ulceration. Considering the good antiulcer activity of amino acids, a series of urea/thiourea derivatives of glutamic acid conjugated benzisothiazole analogue 3a-u with various substituents on aryl ring were synthesized, spectroscopically characterized and evaluated for in vitro H(+)/K(+)-ATPase inhibition. Majority of the compounds possessed potency compared to that of omeprazole, a reference drug. In particular, methoxy derivatives 3p-u were the most active compounds possessing a significant 15-fold increase for para substituent thus, contributing positively to gastric H(+)/K(+)-ATPase inhibition.

Isolation and characterization of antioxidant and antibacterial compound from mango ginger (Curcuma amada Roxb.) rhizome.

The chloroform extract of mango ginger (Curcuma amada Roxb.) rhizome was subjected to antioxidant activity-guided purification by repeated silica gel column chromatography to obtain a pure antioxidant compound. The structure was deduced by analyzing UV, IR, liquid chromatography-mass spectrometry (LC-MS) and two-dimensional heteronuclear multiple quantum coherence transfer spectroscopy (2D-HMQCT) NMR spectral data, and named it as "Amadannulen", a novel compound. It exhibited DPPH radical scavenging activity, super oxide radical scavenging activity, lipid peroxidation inhibitory activity and metal chelating activity. Amadannulen also showed antibacterial activity against both Gram-positive and Gram-negative bacteria tested. It also exhibited bactericidal activity against M. luteus, B. cereus and B. subtilis.

Characterization of an antibacterial peptide from indian cobra (Naja naja) venom

Due to the development of antibiotic resistance in microorganisms, antimicrobial peptides from natural sources have attracted attention in recent times. Several antimicrobial peptides have been isolated from a wide range of animal sources, particularly snake venoms. Naja naja venom showed antibacterial as well as direct and indirect hemolytic activities, and an antibacterial peptide was purified through gel permeation and ion exchange chromatography. Its molecular mass was 2491Da, which was determined using Matrix Assisted Laser Desorption/Ionization-Time-of-Flight (MALDI-TOF) mass spectrometry and the amino acids sequence of the N-terminus was DEQSTHGAYVWKL. The purified peptide showed potent antibacterial activity against Gram-negative and Gram-positive bacterial strains like Escherichia coli, Pseudomonas aeruginosa and Vibrio cholerae, and Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Bacillus subtilis, respectively. The most potent activity was towards Gram-negative bacteria. Activity was retained at concentrations as low as 100µg/ml. Minimum inhibitory concentrations (MIC; in mg) of Naja Antibacterial Peptide (NAP) and known antibiotics against Gram-positive and Gram-negative bacteria were determined using microdilution susceptibility test in sterile 96-well microdilution plates. However, the peptide did not show direct or indirect hemolytic activity.(AU)

Chondroitin sulfate proteoglycans of bovine cornea: structural characterization and assessment for the adherence of Plasmodium falciparum-infected erythrocytes.

The structures of the bovine corneal chondroitin sulfate (CS) chains and the nature of core proteins to which these chains are attached have not been studied in detail. In this study, we show that structurally diverse CS chains are present in bovine cornea and that they are mainly linked to decorin core protein. DEAE-Sephacel chromatography fractionated the corneal chondroitin sulfate proteoglycans (CSPGs) into three distinct fractions, CSPG-I, CSPG-II, and CSPG-III. These CSPGs markedly differ in their CS and dermatan sulfate (DS) contents, and in particular the CS structure-the overall sulfate content and 4- to 6-sulfate ratio. In general, the CS chains of the corneal CSPGs have low to moderate levels (15-64%) of sulfated disaccharides and 0-30% DS content. Structural analysis indicated that the DS disaccharide units in the CS chains are segregated as large blocks. We have also assessed the suitability of the corneal CSPGs as an alternative to placental CSPG or the widely used bovine tracheal chondroitin sulfate A (CSA) for studying the structural interactions involved in the adherence of Plasmodium falciparum-infected red blood cells (IRBCs) to chondroitin 4-sulfate. The data demonstrate that the corneal CSPGs efficiently bind IRBCs, and that the binding strength is either comparable or significantly higher than the placental CSPG. In contrast, the IRBC binding strength of bovine tracheal CSA is markedly lower than the human placental and bovine corneal CSPGs. Thus, our data demonstrate that the bovine corneal CSPG but not tracheal CSA is suitable for studying structural interactions involved in IRBC-C4S binding.

Structure and activity of glycosylphosphatidylinositol anchors of Plasmodium falciparum.

The glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum are thought to be etiologic agents of malaria based on their ability to induce proinflammatory cytokine production by macrophages and cause symptoms that resemble severe malaria illness in animals. This review summarizes the published information on the structures of P. falciparum GPIs, structure-activity relationship, and anti-GPI antibodies in the host.