Synthesis and Pharmacological Investigation of Segetalin C as a Novel Antifungal and Cytotoxic Agent

Rajiv Dahiya; Komalpreet Kaur

doi:10.1055/s-0031-1296463

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2008; 58(1): 29-34
DOI: 10.1055/s-0031-1296463

Antibiotics · Antimycotics · Antiviral Drugs · Chemotherapeutics · Cytostatics

Editio Cantor Verlag Aulendorf (Germany)

Synthesis and Pharmacological Investigation of Segetalin C as a Novel Antifungal and Cytotoxic Agent

Authors

Rajiv Dahiya

¹Pharmaceutical Chemistry Department, Rajiv Academy for Pharmacy, Mathura, Uttar Pradesh, India
Komalpreet Kaur

¹Pharmaceutical Chemistry Department, Rajiv Academy for Pharmacy, Mathura, Uttar Pradesh, India

Abstract

In present study, a natural phenylalanine-rich cycloheptapeptide segetalin C (compound VIII) was synthesized by coupling and cyclization of peptide units Boc-gly-L-leu-L-his-OH and L-Phe-L-ala-L-phe-L-pro-OMe and examined for different bioactivities. The structure of compound VIII was elucidated by IR, ¹H NMR, ¹³C NMR, mass spectral data and elemental analysis. It was demonstrated that the newly synthesized cyclopeptide has good activity against pathogenic fungi Candida albicans and dermatophytes, in addition to high cytotoxicity against Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC) cell lines with CTC₅₀ values of 3.35 and 5.72 µmol/L.

Key words

Antimicrobials - Cytotoxic agents - Heptapeptide, cyclic - Segetalin C, anthelmintic activity, antimicrobial evaluation, cytotoxicity - Vaccaria segetalis

Full Text

References

Literature
1 Roy MK, Thalang VN, Trakoontivakorn G, Nakahara K. Mahanine, a carbazole alkaloid from Micromelum minutum, inhibits cell growth and induces apoptosis in U937 cells through a mitochondrial dependent pathway. Br J Pharmacol. 2005; 145 (2) 145-155
2 Hsieh PW, Chang FR, Wu CC, Wu KY, Li CM, Chen SL et al. New cytotoxic cyclic peptides and dianthramide from Dianthus superbus. J Nat Prod. 2004; 67 (9) 1522-1527
3 Tiew P, Ioset JR, Kokpol U, Chavasiri W, Hostettmann K. Antifungal, antioxidant and larvicidal activities of compounds isolated from the heartwood of Mansonia gagei. Phytother Res. 2003; 17 (2) 190-193
4 Zamilpa A, Tortoriello J, Navarro V, Delgado G, Alvarez L. Antispasmodic and antimicrobial diterpenic acids from Viguiera hypargyrea roots. Planta Med. 2002; 68 (3) 281-283
5 Tan NH, Zhou J. Plant Cyclopeptides. Chem Rev. 2006; 106 (3) 840-895
6 Morel AF, Maldaner G, Ilha V, Missau F, Silva UF, Dalcol II. Cyclopeptide alkaloids from Scutia buxifolia Reiss and their antimicrobial activity. Phytochemistry. 2005; 66 (21) 2571-2576
7 Jennings C, West J, Waine C, Craik D, Anderson M. Biosynthesis and insecticidal properties of plant cyclotides: the cyclic knotted proteins from Oldenlandia affinis. Proc Natl Acad Sci U S A. 2001; 98 (19) 10614-10619
8 Mongkolvisut W, Sutthivaiyakit S, Leutbecher H, Mika S, Klaiber I, Moller W et al. Integerrimides A and B, cyclic heptapeptides from the latex of Jatropha integerrima. J Nat Prod. 2006; 69 (10) 1435-1441
9 Picur B, Cebrat M, Zabrocki J, Siemion IZ. Cyclopeptides of Linum usitatissimum. J Pept Sci. 2006; 12 (9) 569-574
10 Morita H, Iizuka T, Choo CY, Chan KL, Itokawa H, Takeya K. Dichotomins J and K, vasodilator cyclic peptides from Stellaria dichotoma. J Nat Prod. 2005; 68 (11) 1686-1688
11 Morita H, Kayashita T, Kobata H, Gonda A, Takeya K, Itokawa H. Pseudostellarins D-F, new tyrosinase inhibitory cyclic peptides from Pseudostellaria heterophylla. Tetrahedron. 1994; 50 (33) 9975-9982
12 Yun YS, Morita H, Takeya K, Itokawa H. Cyclic peptides from higher plants. 34. Segetalins G and H, structures and estrogen-like activity of cyclic pentapeptides from Vaccaria segetalis. J Nat Prod. 1997; 60 (3) 216-218
13 Morita H, Yun YS, Takeya K, Itokawa H, Yamada K. Segetalins B, C and D, three new cyclic peptides from Vaccaria segetalis. Tetrahedron. 1995; 51 (21) 6003-6014
14 Dahiya R. Synthesis, Characterization and Biological Evaluation of a Glycine-Rich Peptide – Cherimolacyclopeptide E. J Chil Chem Soc. 2007; 52 (3) 1224-1229
15 Dahiya R. Synthetic and Pharmacological Studies on Longicalycinin A. Pak J Pharm Sci. 2007; 20 (4) 317-323
16 Dahiya R, Kaur K. Synthetic and Biological Studies on Natural Cyclic Heptapeptide: Segetalin E. Arch Pharm Res. 2007; 30 (11) 1380-1286
17 Dahiya R, Pathak D. First total synthesis and biological evaluation of halolitoralin A. J Serb Chem Soc. 2007; 72 (2) 101-107
18 Dahiya R, Pathak D. Synthesis, Characterization and Biological Evaluation of Halolitoralin B – A Natural Cyclic Peptide. Asian J Chem. 2007; 19 (2) 1499-1505
19 Dahiya R, Pathak D, Himaja M, Bhatt S. First total synthesis and biological screening of hymenamide E. Acta Pharm. 2006; 56 (4) 399-415
20 Dahiya R, Pathak D. Synthetic Studies on a Natural Cyclic Tetrapeptide – Halolitoralin C. J Pharm Res. 2006; 5 (3) 69-73
21 Dahiya R, Pathak D. Cyclic Peptides: New Hope for Antifungal Therapy. Egypt Pharm J (NRC). 2006; 5 (2) 189-199
22 Pathak D, Dahiya R. Cyclic Peptides as Novel Antineoplastic Agents: A Review. J Sci Pharm. 2003; 4 (4) 125-131
23 Bodanszky M, Bodanszky A. eds. The Practice of Peptide Synthesis. New York: Springer-Verlag; 1984: 78-143
24 Bauer AW, Kirby WM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Path. 1966; 45: 493-496
25 Garg LC, Atal CK. Anthelmintic activity of Myrsine Africana. Indian J Pharm Sci. 1963; 59: 240-245
26 Kuttan R, Bhanumathy P, Nirmala K, George MC. Potential anticancer activity of turmeric (Curcuma longa). Cancer Lett. 1985; 29 (2) 197-202