Login Register Cart 0
Generic placeholder image

Current Organic Synthesis

Editor-in-Chief

ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Towards the Synthesis of a Heterocyclic Analogue of Natural Cyclooligopeptide with Improved Bio-properties

Author(s): Rajiv Dahiya*, Sunita Dahiya, Suresh V. Chennupati, Vernon Davis, Vijaya Sahadeo and Jayvadan K. Patel

Volume 19, Issue 2, 2022

Published on: 26 November, 2021

Page: [267 - 278] Pages: 12

DOI: 10.2174/1570179418666211005141811

Price: $65

Abstract

Aims: The present investigation is targeted towards the synthesis of a novel analogue of a natural peptide of marine origin. Background: Marine sponges are enriched with bioactive secondary metabolites, especially circu-lar peptides. Heterocycles are established organic compounds with potential biological value. Tak-ing into consideration the bio-properties of heterocycles and marine sponge-derived natural pep-tides, an effort was made for the synthesis of a heterocyclic analogue of a natural cyclopeptide.

Objective: A heterocyclic analogue of a sponge-derived proline-containing cyclic peptide, rolloam-ide A, was synthesized by interaction of Boc-protected L-histidinyl-L-prolyl-L-valine and L-prolyl-L-leucyl-L-prolyl-L-isoleucine methyl ester and compared with synthetic rolloamide A with bioac-tivity against bacteria, fungi, and earthworms.

Methods: The synthesis of cycloheptapeptide was accomplished employing the liquid phase method. The larger peptide segment was prepared by interaction of Boc-protected L-prolyl-L-leu-cine with L-prolyl-L-isoleucine methyl ester. Similarly, the tripeptide unit was synthesized from Boc-protected L-histidinyl-L-proline with L-valine ester. The linear heptapeptide segment (7) was cyclized by utilizing pentafluorophenyl (pfp) ester, and the structure was elucidated by elemental and spectral (IR, 1H/13C NMR, MS) analysis. The peptide was also screened for diverse bioactivities such as antibacterial, antifungal, and potential against earthworms and cytotoxicity.

Results: The novel cyclooligopeptide was synthesized with 84% yield by making use of car-bodiimides. The synthesized cyclopeptide exhibited significant cytotoxicity against two cell lines. In addition, promising antifungal and antihelmintic properties were observed for newly synthesized heterocyclic peptide derivative (8) against dermatophytes and three earthworm species at 6 μg/mL and 2 mg/mL, respectively.

Conclusion: Solution-phase technique employing carbodiimide chemistry was established to be promising for synthesizing the cycloheptapeptide derivative (8), and C5H5N was proved to be a better base for heptapeptide circling when compared to N-methylmorpholine and triethylamine.

Keywords: Cyclopeptide, heterocycle, sponge, peptide synthesis, cyclization, biopotential.

« Previous Next »
Graphical Abstract

[1]
Arora, P.; Arora, V.; Lamba, H.S.; Wadhwa, D. Importance of heterocyclic chemistry: A review. Int. J. Pharm. Res. Sci., 2012, 3, 2947-2955.
[2]
Kaushik, C.P.; Sangwan, J.; Luxmi, R.; Kumar, K.; Pahwa, A. Synthetic routes for 1,4-disubstituted 1,2,3-triazoles: A review. Curr. Org. Chem., 2019, 23, 860-900.
[http://dx.doi.org/10.2174/1385272823666190514074146]
[3]
Mondal, A.; Banerjee, B.; Bhaumik, A.; Mukhopadhyay, C. Activated alumina balls under neat conditions: A green catalyst for the synthesis of spiro-heterocyclic scaffolds by ring-opening versus annulation of the isatin moiety. ChemCatChem, 2016, 8, 1185-1198.
[http://dx.doi.org/10.1002/cctc.201500885]
[4]
Esmaeilpour, M.; Javidi, J.; Divar, M. A green one-pot three-component synthesis of spirooxindoles under conventional heating conditions or microwave irradiation by using. Fe3O4@SiO2-imid-PMAn magnetic porous nanospheres as a recyclable catalyst. J. Magn. Magn. Mater., 2017, 423, 232-240.
[http://dx.doi.org/10.1016/j.jmmm.2016.09.020]
[5]
Esmaeilpour, M.; Javidi, J. Fe3O4@SiO2-imid-PMAn magnetic porous nanosphere as reusable catalyst for synthesis of polysubstituted quinolines under solvent-free conditions. J. Chin. Chem. Soc. (Taipei), 2015, 62, 328-334.
[http://dx.doi.org/10.1002/jccs.201400380]
[6]
Roy, R.S.; Gehring, A.M.; Milne, J.C.; Belshaw, P.J.; Walsh, C.T. Thiazole and oxazole peptides: Biosynthesis and molecular machinery. Nat. Prod. Rep., 1999, 16(2), 249-263.
[http://dx.doi.org/10.1039/a806930a] [PMID: 10331285]
[7]
Hamdan, F.; Tahoori, F.; Balalaie, S. Synthesis of novel cyclopeptides containing heterocyclic skeletons. RSC Adv., 2018, 8, 33893-33926.
[http://dx.doi.org/10.1039/C8RA03899F]
[8]
Bertram, A.; Hannam, J.S.; Jolliffe, K.A.; González-López de Turiso, F.; Pattenden, G. The synthesis of novel thiazole containing cyclic peptides via cyclooligomerisation reactions. Synlett, 1999, 1999, 1723-1726.
[http://dx.doi.org/10.1055/s-1999-2942]
[9]
Fang, W.Y.; Dahiya, R.; Qin, H.L.; Mourya, R.; Maharaj, S. Natural proline-rich cyclopolypeptides from marine organisms: Chemistry, synthetic methodologies and biological status. Mar. Drugs, 2016, 14(11), 194.
[http://dx.doi.org/10.3390/md14110194] [PMID: 27792168]
[10]
Dahiya, R.; Dahiya, S. Ocular delivery of peptides and proteins. Drug delivery for the retina and posterior segment disease; Patel, J.K.; Sutariya, V.; Kanwar, J.R; Pathak, Y.V., Ed.; Springer: Cham, Switzerland, 2018, pp. 411-437.
[http://dx.doi.org/10.1007/978-3-319-95807-1_24]
[11]
Fusetani, N.; Matsunaga, S. Bioactive sponge peptides. Chem. Rev., 1993, 93, 1793-1806.
[http://dx.doi.org/10.1021/cr00021a007]
[12]
Vitali, A. Antimicrobial peptides derived from marine sponges. Am. J. Clin. Microbiol. Antimicrob., 2018, 1, 1006.
[13]
Matsunaga, S.; Fusetani, N.; Konosu, S. Bioactive marine metabolites, IV. Isolation and the amino acid composition of discodermin A, an antimicrobial peptide, from the marine sponge Discodermia kiiensis. J. Nat. Prod., 1985, 48(2), 236-241.
[http://dx.doi.org/10.1021/np50038a006] [PMID: 3839260]
[14]
Zhang, X.; Jacob, M.R.; Rao, R.R.; Wang, Y.H.; Agarwal, A.K.; Newman, D.J.; Khan, I.A.; Clark, A.M.; Li, X.C. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani. Res. Rep. Med. Chem., 2013, 3, 9-10.
[15]
Tran, T.D.; Pham, N.B.; Fechner, G.A.; Hooper, J.N.; Quinn, R.J. Potent cytotoxic peptides from the Australian marine sponge Pipestela candelabra. Mar. Drugs, 2014, 12(6), 3399-3415.
[http://dx.doi.org/10.3390/md12063399] [PMID: 24901701]
[16]
Rashid, M.A.; Gustafson, K.R.; Boswell, J.L.; Boyd, M.R. Haligramides A and B, two new cytotoxic hexapeptides from the marine sponge Haliclona nigra. J. Nat. Prod., 2000, 63(7), 956-959.
[http://dx.doi.org/10.1021/np000051+] [PMID: 10924173]
[17]
Suarez-Jimenez, G.M.; Burgos-Hernandez, A.; Ezquerra-Brauer, J.M. Bioactive peptides and depsipeptides with anticancer potential: Sources from marine animals. Mar. Drugs, 2012, 10(5), 963-986.
[http://dx.doi.org/10.3390/md10050963] [PMID: 22822350]
[18]
Wakimoto, T.; Tan, K.; Tajima, H.; Abe, I. Cytotoxic cyclic peptides from the marine sponges. Handbook of anticancer drugs from marine origin; Kim, S.K., Ed.; Springer: Cham, Switzerland, 2015, pp. 113-144.
[http://dx.doi.org/10.1007/978-3-319-07145-9_6]
[19]
Sera, Y.; Adachi, K.; Fujii, K.; Shizuri, Y. A new antifouling hexapeptide from a Palauan sponge, Haliclona sp. J. Nat. Prod., 2003, 66(5), 719-721.
[http://dx.doi.org/10.1021/np020271i] [PMID: 12762818]
[20]
Daletos, G.; Kalscheuer, R.; Koliwer-Brandl, H.; Hartmann, R.; de Voogd, N.J.; Wray, V.; Lin, W.; Proksch, P. Callyaerins from the marine sponge Callyspongia aerizusa: Cyclic peptides with antitubercular activity. J. Nat. Prod., 2015, 78(8), 1910-1925.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00266] [PMID: 26213786]
[21]
Plaza, A.; Bifulco, G.; Keffer, J.L.; Lloyd, J.R.; Baker, H.L.; Bewley, C.A. Celebesides A-C and theopapuamides B-D, depsipeptides from an Indonesian sponge that inhibit HIV-1 entry. J. Org. Chem., 2009, 74(2), 504-512.
[http://dx.doi.org/10.1021/jo802232u] [PMID: 19072692]
[22]
Yamano, Y.; Arai, M.; Kobayashi, M. Neamphamide B, new cyclic depsipeptide, as an anti-dormant mycobacterial substance from a Japanese marine sponge of Neamphius sp. Bioorg. Med. Chem. Lett., 2012, 22(14), 4877-4881.
[http://dx.doi.org/10.1016/j.bmcl.2012.05.071] [PMID: 22704240]
[23]
Williams, D.E.; Yu, K.; Behrisch, H.W.; Van Soest, R.; Andersen, R.J. Rolloamides A and B, cytotoxic cyclic heptapeptides isolated from the Caribbean marine sponge Eurypon laughlini. J. Nat. Prod., 2009, 72(7), 1253-1257.
[http://dx.doi.org/10.1021/np900121m] [PMID: 19583251]
[24]
Belagali, S.L.; Himaja, M.; Kumar, L.H.; Thomas, R.; Prakasini, S.R.; Poojary, B. (Nitro) hymenamide A, unusual biologically active cyclic peptide. Boll. Chim. Farm., 1999, 138(4), 160-164.
[PMID: 10422327]
[25]
Shinde, N.V.; Himaja, M.; Bhosale, S.K.; Ramana, M.V.; Sakarkar, D.M. Synthesis and biological evaluation of delavayin-C. Indian J. Pharm. Sci., 2008, 70(6), 827-831.
[http://dx.doi.org/10.4103/0250-474X.49137] [PMID: 21369456]
[26]
Poojary, B.; Kumar, K.H.; Belagali, S.L. Synthesis and biological evaluation of pseudostellarin B. Farmaco, 2001, 56(4), 331-334.
[http://dx.doi.org/10.1016/S0014-827X(01)01031-X] [PMID: 11421263]
[27]
Poojary, B.; Belagali, S.L. Synthetic studies on cyclic octapeptides: Yunnanin F and Hymenistatin. Eur. J. Med. Chem., 2005, 40(4), 407-412.
[http://dx.doi.org/10.1016/j.ejmech.2004.11.013] [PMID: 15804540]
[28]
Hawkins, P.M.E.; Tran, W.; Nagalingam, G.; Cheung, C.Y.; Giltrap, A.M.; Cook, G.M.; Britton, W.J.; Payne, R.J. Total synthesis and antimycobacterial activity of ohmyungsamycin A, deoxyecumicin, and ecumicin. Chemistry, 2020, 26(66), 15200-15205.
[http://dx.doi.org/10.1002/chem.202002408] [PMID: 32567168]
[29]
Hughes, R.A.; Moody, C.J. From amino acids to heteroaromatics--thiopeptide antibiotics, nature’s heterocyclic peptides. Angew. Chem. Int. Ed., 2007, 46(42), 7930-7954.
[http://dx.doi.org/10.1002/anie.200700728] [PMID: 17854013]
[30]
Luesch, H.; Williams, P.G.; Yoshida, W.Y.; Moore, R.E.; Paul, V.J. Ulongamides A-F, new beta-amino acid-containing cyclodepsipeptides from Palauan collections of the marine Cyanobacterium lyngbya sp. J. Nat. Prod., 2002, 65(7), 996-1000.
[http://dx.doi.org/10.1021/np0200461] [PMID: 12141859]
[31]
Dahiya, S.; Dahiya, R. A comprehensive review of chemistry and pharmacological aspects of natural cyanobacterial azoline-based circular and linear oligopeptides. Eur. J. Med. Chem., 2021, 218113406
[http://dx.doi.org/10.1016/j.ejmech.2021.113406] [PMID: 33823395]
[32]
Bodanzsky, M.; Bodanzsky, A. The Practice of Peptide Synthesis; Springer-Verlag: New York, 1984.
[http://dx.doi.org/10.1007/978-3-642-96835-8]
[33]
Bauer, A.W.; Kirby, W.M.; Sherris, J.C.; Turck, M. Antibiotic susceptibility testing by a standardized single disk method. Am. J. Clin. Pathol., 1966, 45(4), 493-496.
[http://dx.doi.org/10.1093/ajcp/45.4_ts.493] [PMID: 5325707]
[34]
Garg, L.C.; Atal, C.K. Anthelmintic activity of Myrsine africana. Indian J. Pharm. Sci., 1963, 59, 240-245.
[35]
Kuttan, R.; Bhanumathy, P.; Nirmala, K.; George, M.C. Potential anticancer activity of turmeric (Curcuma longa). Cancer Lett., 1985, 29(2), 197-202.
[http://dx.doi.org/10.1016/0304-3835(85)90159-4] [PMID: 4075289]
[36]
Dahiya, R. Synthesis and in vitro cytotoxic activity of a natural peptide of plant origin. J. Iranian Chem. Soc., 2008, 5, 445-452.
[http://dx.doi.org/10.1007/BF03246001]
[37]
Dahiya, R.; Kumar, A.; Yadav, R. Synthesis and biological activity of peptide derivatives of iodoquinazolinones/nitroimidazoles. Molecules, 2008, 13(4), 958-976.
[http://dx.doi.org/10.3390/molecules13040958] [PMID: 18463598]
[38]
Dahiya, R.; Pathak, D. Synthetic studies on novel benzimidazolopeptides with antimicrobial, cytotoxic and anthelmintic potential. Eur. J. Med. Chem., 2007, 42(6), 772-798.
[http://dx.doi.org/10.1016/j.ejmech.2006.11.015] [PMID: 17239491]
[39]
Dahiya, R.; Singh, S. Toward the synthesis and pharmacological screening of a natural cycloheptapeptide of plant origin. Nat. Prod. Commun., 2017, 12(3), 379-383.
[http://dx.doi.org/10.1177/1934578X1701200318] [PMID: 30549890]

Rights & Permissions Print Cite
Article Metrics
22
1
© 2024 Bentham Science Publishers | Privacy Policy