58872-03-0Relevant articles and documents
Effect of Low Charge and High Hydrophobicity on Antimicrobial Activity of the Quinazolinone-Peptide Conjugates
Rakesh, Kadallipura Puttaswamy,Ramesh, Suhas,Shivakumar,Gowda, Dase Channe
, p. 158 - 164 (2018/04/23)
Peptides of relatively low charge and a high number of hydrophobic amino acids were designed. The amino acid sequence of designed peptides was GXGVP, where X equaled to W, Y, F, D, and T with a combination of hydrophobic, charged and polar units. These peptides were linked to quinazolinones to obtain a new class of compounds with synergistic features. The hybrids displayed antimicrobial activity against Gram-positive and Gram-negative bacteria. In particular, Trp, Tyr, and Phe-containing peptides showed greater antimicrobial potency than the reference standards. Alkyl chain length variations in heterocyclic moiety indicated that hybrids with propyl group were more active than butyl derivatives. Improved results were observed for debenzylated versions of the conjugates compared to their benzylated counterparts. Implementation of the hybrid structures of varying charge, hydrophobicity, and alkyl chain length would be a promising approach to obtaining effective antimicrobial agents.
Anti-inflammatory and Antioxidant Peptide-Conjugates: Modulation of Activity by Charged and Hydrophobic Residues
Rakesh,Suhas,Gowda, D. Channe
, p. 1 - 8 (2018/01/04)
In the present study, antioxidant and anti-inflammatory activities of a series of quinazolinone-conjugated-peptides were investigated. Substitution of second position of the peptide template ‘GXGVP’ by different amino acids of varying hydrophobicity, charge and polarity has been studied. Quinazolinone-peptides with Trp residue emerged out as the highly potential antioxidant whereas the conjugate with Asp moiety turned to be a good anti-inflammatory agent. These data indicate that more hydrophobicity favours antioxidant property and contrarily, presence of charged species in the molecule assists the reduction of inflammation. Further, conjugates having butyl group in the heterocyclic part and free C-terminus in the peptide part exhibited good inflammation reducing property. Thus, variation of hydrophobic groups, charges and polarity of certain amino acids in the peptide segment of the conjugate could be used to develop “dual war-head” potential therapeutics for treating inflammation and allied diseases.
Inhibition of urease enzyme activity by urea and thiourea derivatives of dipeptides conjugated 2, 3-dichlorophenyl piperazine
Suyoga Vardhan,Kumara,Pavan Kumar,Channe Gowda
, p. 92 - 99 (2017/09/11)
Objective: Studies on enzyme inhibition remain an important area of pharmaceutical research since these studies have led to the discoveries of drugs used in a variety of physiological conditions. In search of novel urease enzyme inhibitors, four dipeptide
Structure-Based Rationale Design and Synthesis of Aurantiamide Acetate Analogues - Towards a New Class of Potent Analgesic and Anti-inflammatory Agents
Suhas, Ramesh,Channe Gowda, Dase
experimental part, p. 850 - 862 (2012/06/04)
A series of new aurantiamide acetate analogues were synthesized by modifying its N-terminal substitution and the amino acid residue. The structure of all these compounds was established on the basis of analytical and spectral studies. All the new derivatives were evaluated in vivo for their analgesic activity by tail flick method in mice and anti-inflammatory activity against carrageenan-induced oedema in albino rats at different doses (25, 50 and 100mg/kg body weight). All the compounds exhibited significant pharmacological activity with no ulcerogenic liability. In particular, pentapeptides and tricosamers (30 amino acids) containing analogues have demonstrated high potency than the reference standards. These compounds hold promise for further development.
Design and synthesis of tryptophan containing peptides as potential analgesic and anti-inflammatory agents
Suhas,Gowda, D.Channe
scheme or table, p. 535 - 540 (2012/09/22)
A new series of smaller peptides with tryptophan at C-terminal and varying N-protected amino acids/peptides were designed, synthesized and characterized by analytical and spectroscopic techniques. Analgesic and anti-inflammatory properties of these peptides were carried out in vivo using tail-flick method and carrageenan-induced paw edema method, respectively, at different doses and different time intervals. Most of the peptides synthesized displayed enhanced activity, and particularly tetra and hexapeptides 29-31 were found to be even more potent than the reference standards used. Moreover, some peptides have exhibited promising activity even after 24h of administration, whereas the reference standards were active only up to 3h. Further, the compounds did not present any ulcerogenic liability.
Design, synthesis and evaluation of monovalent Smac mimetics that bind to the BIR2 domain of the anti-apoptotic protein XIAP
González-Lpez, Marcos,Welsh, Kate,Finlay, Darren,Ardecky, Robert J.,Ganji, Santhi Reddy,Su, Ying,Yuan, Hongbin,Teriete, Peter,MacE, Peter D.,Riedl, Stefan J.,Vuori, Kristiina,Reed, John C.,Cosford, Nicholas D.P.
scheme or table, p. 4332 - 4336 (2011/08/06)
We report the systematic rational design and synthesis of new monovalent Smac mimetics that bind preferentially to the BIR2 domain of the anti-apoptotic protein XIAP. Characterization of compounds in vitro (including 9i; ML101) led to the determination of key structural requirements for BIR2 binding affinity. Compounds 9h and 9j sensitized TRAIL-resistant breast cancer cells to apoptotic cell death, highlighting the value of these probe compounds as tools to investigate the biology of XIAP.
Novel C2-C3′ N-peptide linked macrocyclic taxoids. Part 2: Synthesis and biological activities of docetaxel analogues with a peptide side chain at C2 and their macrocyclic derivatives
Larroque, Anne-Laure,Dubois, Joelle,Thoret, Sylviane,Aubert, Genevieve,Chiaroni, Angele,Gueritte, Francoise,Guenard, Daniel
, p. 563 - 574 (2008/03/12)
The synthesis of a series of novel docetaxel analogues possessing a peptide side chain at the C2 position as well as peptide macrocyclic taxoids is described. These compounds were designed to mimic a region of the α-tubulin loop equivalent to the paclitax
N-bromosuccinimide oxidation of dipeptides and their amino acids: Synthesis, kinetics and mechanistic studies
Linge Gowda,Kumara,Channe Gowda,Rangappa
, p. 376 - 385 (2008/02/08)
Dipeptides (DP), namely valyl-glycine (Val-Gly), alanyl-proline (Ala-Pro), and valyl-proline (Val-Pro) were synthesized by classical solution phase methods and characterized. The kinetics of oxidation of amino acids (AA) and DP by N-bromosuccinimide (NBS) was studied in the presence of perchlorate ions in acidic medium at 28°C. The reaction was followed spectrophotometrically at λmax = 240 nm. The reactions follow identical kinetics, being first order each in [NBS], [AA], and [DP]. No effect on [H+], reduction product [succinimide], and ionic strength was observed. Effects of varying dielectric constant of the medium and addition of anions such as chloride and perchlorate were studied. Activation parameters have been computed. The oxidation products of the reaction were isolated and characterized. The proposed mechanism is consistent with the experimental results. An apparent correlation was noted between the rate of oxidation of AA and DP.
Synthesis and crystal structure of tripeptide fragment of elastin
Doreswamy,Mahendra,Abiraj,Gowda, D. Channe,Sridhar,Prasad, J. Shashidhara
, p. 829 - 833 (2007/10/03)
Boc-Gly-Val-Pro-OBzl, a protected tripeptide fragment of repeating sequences of mammalian elastic protein elastin was synthesized and characterized by X-ray diffraction method. The sequence C24 H35 N 3 O6 crysta
Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer
Oost, Thorsten K.,Sun, Chaohong,Armstrong, Robert C.,Al-Assaad, Ali-Samer,Betz, Stephen F.,Deckwerth, Thomas L.,Ding, Hong,Elmore, Steven W.,Meadows, Robert P.,Olejniczak, Edward T.,Oleksijew, Andrew,Oltersdorf, Tilman,Rosenberg, Saul H.,Shoemaker, Alexander R.,Tomaselli, Kevin J.,Zou, Hua,Fesik, Stephen W.
, p. 4417 - 4426 (2007/10/03)
Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogues that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small molecule XIAP antagonists as a potential therapy for cancers that overexpress XIAP.
