Medicinal Chemistry Research

, Volume 22, Issue 1, pp 1–15 | Cite as

Vasicine and structurally related quinazolines

  • Kunal Nepali
  • Sahil Sharma
  • Ritu Ojha
  • Kanaya Lal Dhar
Review Article


Natural products are diverse sources of important chemical constituents. Most of the metabolites isolated from them are heterocycles possessing diverse pharmacological actions. Vasicine, a heterocyclic alkaloid possessing a privileged quinazoline nucleus is primarily present in the leaves o the plant Adhatoda vasica nees, family Acanthaceae. Vasicine and structurally related quinazolines have been an area of interest for the researchers all around the world. The present review provides an up to date compilation of the alkaloid vasicine, its biosynthesis, synthesis, biological attributes, design of its synthetic analogues along with structurally related quinazolines.


Quinazoline Antitussive Synthesis Bronchodilator Alkaloid 


  1. Ali M (1998) Textbook of pharmacognosy, 1st edn. CBS Publishers and Distributors, New DelhiGoogle Scholar
  2. Amin AH, Mehta DR, Samarth SS (1963) Proceedings First Intern. Pharmacological Meeting Stockholm. Pergamon Press Ltd, OxfordGoogle Scholar
  3. Atal CK (1980) Chemistry and pharmacology of vasicine—a new oxytocic and abortifacient. Raj Bandhu Industrial Co, New Delhi, p 148Google Scholar
  4. Atal CK, Sharma RL, Dhar KL (1979) Chemistry and pharmacology of vasicine—a new oxytocic & abortifacient synthesis of deoxydihomo “C” vasicinone. Indian J Chem 18b:444–450Google Scholar
  5. Bagchi GD, Dwivedi PD, Haider F, Singh S, Srivastava S, Chattopadhyay SK (2003) Seasonal variation in VASICINE contents in Adhatoda species grown under north Indian plain conditions. J Med Arom Plants 25:37–40Google Scholar
  6. Bhide MB, Naik PV, Ghooi RB (1974) Studies on the pharmacological evaluation of vasicine and vasicinone. In: Xth Scientific Seminar in Indian Medicine Institute of Medical Sciences, Banaras Hindu University, Banaras, IndiaGoogle Scholar
  7. Bhide MB, Naik PV, Haramsheth DR (1976) Recent advances in pharmacology of antiasthmatic drugs of Indian origin. In: U.G.C. Seminar on Recent advances in chemistry and pharmacology of Indian plant drugs, Vishakapatnam, IndiaGoogle Scholar
  8. Bowman WR, Elsegood MRJ, Stein T, Weaver GW (2007) Radical reactions with 3H-quinazolin-4-ones: synthesis of deoxyvasicinone, mackinazolinone, luotonin A, rutaecarpine and tryptanthrin. Org Biomol Chem 5:103–113PubMedCrossRefGoogle Scholar
  9. Cambridge GW, Jansen ABA, Jarman DA (1962) Bronchodilating action of vasicinone and related compounds. Nature 196:1217PubMedCrossRefGoogle Scholar
  10. Chan WY, Connel MO, Pomery SR (1963) Effects of the estrous cycle on the sensitivity of rat uterus to oxytocin and desamino-oxytocin. Endrocrinology 72:279CrossRefGoogle Scholar
  11. Chandhok N, Gupta OP, Atal CK (1978) Abortifacient activity of the alkaloid vasicine through the release of prostaglandins. J Steroid Biochem 9:885CrossRefGoogle Scholar
  12. Chattopadhyay SK, Bagchi GD, Dwivedi PD, Srivastava S (2003) Process for the production of vasicine. United States Patent 6676976Google Scholar
  13. Chopra RN (1982) Indigenous drugs of India. Academic Publishers, CalcuttaGoogle Scholar
  14. Chopra R, Ghosh S (1925) Some observations on the pharmacological actions and therapeutic properties of Adhatoda vasica. Indian J Med Res 13:205–212Google Scholar
  15. Collier HOJ, Holgate JA, Schachter M, Shorley PG (1960) The bronchoconstrictor action of bradykinin in the guinea-pig. Br J Pharmacol 15:290Google Scholar
  16. Deetz MJ, Malerich JP, Beatty AM, Smith BD (2001) One-step synthesis of 4(3H) quinazolinones. Tetrahedron Lett 42:1851–1854CrossRefGoogle Scholar
  17. Dhar KL, Jain MP, Koul SK, Atal CK (1981) Vasicol, a new alkaloid from Adhatoda vasica. Phytochemistry 20:319CrossRefGoogle Scholar
  18. Eguchi S, Suzuki T, Okawa T, Matsushita Y (1996) Synthesis of optically active vasicinone based on intramolecular aza-Wittig reaction and asymmetric oxidation. J Org Chem 61:7316–7319PubMedCrossRefGoogle Scholar
  19. Fitzgerald JS, Johns SR, Lamberton JA, Redcliffe AH (1966) 6,7,8,9-Tetrahydropyridoquinazolines, a new class of alkaloids from Mackinlaya species (Araliaceae). Aust J Chem 19:151CrossRefGoogle Scholar
  20. Ghose TP, Krishna S, Narang KS, Ray JN (1932) Vasicine. J Chem Soc 2740:105Google Scholar
  21. Grange JM, Snell NJ (1996) Activity of bromhexine and ambroxol, semi-synthetic derivatives of vasicine from the Indian shrub Adhatoda vasica against Mycobacterium tuberculosis in vitro. J Ethnopharmacol 50:49–53PubMedCrossRefGoogle Scholar
  22. Groger D, Mornas K (1960) On the biogenesis of peganine. Arch Pharm 293:1049–1052CrossRefGoogle Scholar
  23. Gupta KC, Chopra IC (1954) Antitubercular effect of an extract of Adhatoda vasica. Nature 173:1194CrossRefGoogle Scholar
  24. Gupta OP, Sharma ML, Ghatak Ray BJ, Atal CK (1977) Potent uterine activity of alkaloid vasicine. J Med Res 66:680Google Scholar
  25. Gupta OP, Anand KK, Ghatak BJR, Atal CK (1978) Apromising uterotonic abortifacient. Indian J Exp Biol 16:1075–1077PubMedGoogle Scholar
  26. Ho YL, Chang YS (2002) Studies on the antinociceptive, anti-inflammatory and anti pyretic effects of Isatis indigotica root. Phytomedicine 9:419–424PubMedCrossRefGoogle Scholar
  27. Hooper ID (1888) Isoln from Adhatoda vasica Nees, Acanthaceae. J Pharm 18:841–842Google Scholar
  28. Jain MP, Sharma VK (1982) Phytochemical investigation of roots of Adhatoda vasica. Planta Med 46:250PubMedCrossRefGoogle Scholar
  29. Jindal DP, Bhatti RS, Ahlawat S, Gupta S (2002) Synthesis and bronchodilatory activity of some nitrogen bridgehead compounds. Eur J Med Chem 37:419–425PubMedCrossRefGoogle Scholar
  30. Johne S, Groger D (1968) Investigation in the biosynthesis of peganines (vasicine) Engl Sum. Phytochemistry 7:429CrossRefGoogle Scholar
  31. Johne S, Groger D, Richter G (1968) Contribution to the biosynthesis of peganine in Adhatoda vasica-D alkaloid inst auto radiography succinic-acid malic-acid aspartic-acid anthranilic-acid glutamine amino-acids. Arch Pharm 301:721CrossRefGoogle Scholar
  32. Johns SR, Lamberton JA (1965) Alkaloids of Mackinlaya species (Family Araliaceae). Chem Commun 267:83Google Scholar
  33. Joshi BS, Bai Y, Puar MS, Dubose KK, Pelletier SW (1994) 1H and 13C-NMR assignments for some pyrrole [2,b]-quinazoline alkaloids of A. vasica. J Nat Prod 57:953–996CrossRefGoogle Scholar
  34. Joshi BS, Newton MG, Lee DW, Barber AD, Pelletier SW (1996) Reversal of absolute stereochemistry of the pyrrolo [2,1-b]quinazoline alkaloids vasicine, vasicinone, vasicinol and vasicinolone. Tetrahedron Asymmetry 7:25–28CrossRefGoogle Scholar
  35. Kamal A, Ramana KV, Rao MV (2001) Chemoenzymatic synthesis of pyrrolo[2,1-b]quinazolinones: lipase-catalyzed resolution of vasicinone. J Org Chem 66:997-1001PubMedCrossRefGoogle Scholar
  36. Kamal A, Ramana AV, Reddy KS, Ramana KV, Babu AH, Prasad BR (2004) One pot conversion of azido arenes to N-arylacetamides and N-arylformamides: synthesis of 1,4-benzodiazepine-2,5-diones and fused [2,1-b]quinazolinones. Tetrahedron Lett 45:8187–8190CrossRefGoogle Scholar
  37. Kametani T, Loc CV, Higa T, Koizumi M, Ihara M, Fukumoto K (1977) Iminoketene cycloaddition. 2. Total syntheses of arborine, glycosminine, and rutecarpine by condensation of iminoketene with amides. J Am Chem Soc 99:2306CrossRefGoogle Scholar
  38. Lahiri PK, Pradhan SN (1964) Pharmacological investigation of vasicinol an alkaloid from Adhatoda vasica Nees. Indian J Exp Biol 2:219Google Scholar
  39. Lee ES, Park J, Jahng Y (2003) A facile synthesis of simple alkaloids-synthesis of 2,3-polymethylene-4(3H)-quinazolinones and related alkaloids. Tetrahedron Lett 44:1883–1886CrossRefGoogle Scholar
  40. Leete E (1967) Biogenesis of natural compounds. Pergamon press, OxfordGoogle Scholar
  41. Leonard NJ, Martell MJ (1960) Laboratory realization of the Schőpf-Oechler scheme of vasicine synthesis. Tetrahedron Lett 1:44Google Scholar
  42. Liljegren DR (1968) The biosynthesis of quinazoline alkaloids of Peganum harmala L. Phytochemistry 7:1299CrossRefGoogle Scholar
  43. Liljegren DR (1971) Biosynthesis of quinazoline alkaloids of Peganum harmala. Phytochemistry 10:2661–2669CrossRefGoogle Scholar
  44. Liu J, Ye P, Sprague K, Sargent K, Yohannes D, Baldino CM, Wilson CJ, Shi-Chung NG (2005) Novel one-pot total syntheses of deoxyvasicinone, mackinazolinone, isaindigotone, and their derivatives promoted by microwave irradiation. Org Lett 7:3363–3366PubMedCrossRefGoogle Scholar
  45. Mahindroo N, Zabeer A, Bhagat A, Bedi KL, Khajuria KR, Kapoor VK, Dhar KL (2005 ) Synthesis and structure-activity relationships of vasicine analogues as bronchodilatory agents. Med Chem Res 14:347–368CrossRefGoogle Scholar
  46. Maikhuri RK, Gangwar AK (1965) Ethnobiological notes on the Khasi and Garo tribes of Meghalaya Northeast India. Econ Bot 47:345CrossRefGoogle Scholar
  47. Manske RHF, Holmes HL (1953) The alkaloids. Incorporated Publishers, New YorkGoogle Scholar
  48. Manske RHF, Holmes HL (1972–1976) The alkaloids. Incorporated Publishers, New YorkGoogle Scholar
  49. Mehta DR, Naravane JS, Desai RM (1963) Vasicinone. A bronchodilator principle from Adhatoda vasica Nees (N. O. Acanthaceae). J Org Chem 28:445CrossRefGoogle Scholar
  50. Meindl WR, von Angerer E, Schonenberger H, Ruckdeschel G (1984) Benzylamines: synthesis and evaluation of antimycobacterial properties. J Med Chem 27:1111–1118PubMedCrossRefGoogle Scholar
  51. Mohrle H, Gundlach P (1970) Eine neue synthese für dl-vasicin. Tetrahedron Lett 11:3249CrossRefGoogle Scholar
  52. Molina P, Ta ′ rraga A, Gonzalez-Tejero A, Rioja I, Ubeda A, Terencio MC, Alcaraz MJ (2001) Inhibition of leukocyte functions by the alkaloid isaindigotone from Isatis indigotica and some new synthetic derivatives. J Nat Prod 64:297–1300CrossRefGoogle Scholar
  53. Mooris RC, Hanford WE, Adams R (1935) Structure of vasicine. III. Position of the hydroxyl group. J Am Chem Soc 57:951–954CrossRefGoogle Scholar
  54. Nepali K, Bande MS, Sapra S, Garg A, Kumar S, Sharma P, Goyal R, Satti NK, Suri OP, Dhar KL (2010) Antitussive effects of azepino[2,1-b]quinazolones. Med Chem Res. doi: 10.1007/s00044-011-9641-1
  55. Pan L, Tan J, Hou J, Huang S, Gu L, Huang Z (2008) Design, synthesis and evaluation of isaindigotone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors. Bioorg Med Chem Lett 18:3790–3793PubMedCrossRefGoogle Scholar
  56. Pandita K, Bhatia MS, Thappa RK, Agarwal SG, Dhar KL, Atal CK (1983) Seasonal variation of alkaloids of Adhatoda vasica and detection of glycosides and N-oxides of vasicine and vasicinone. Planta Med 48:81–82PubMedCrossRefGoogle Scholar
  57. Piacenza F (1966) Desirable side effects of an expectorant. Deutsche Med J 17:226–228Google Scholar
  58. Reynolds TM, Robinson R (1934) Constitution of vasicine. Nature 134:142CrossRefGoogle Scholar
  59. Satakopan S, Thomas PJ (1970) Note on adulterant of vasaka. Indian J Pharm 32:66–67Google Scholar
  60. Schopf C, Oechler F (1936) Zur Frage der Biogenese des Vasicins (Peganins). Die Synthese des Desoxyvasicins unter physiologischen Bedingungen. Justus Liebigs Ann Chem 523:1–29CrossRefGoogle Scholar
  61. Sen JN, Ghose TP (1924) Alkaloid from leaves of Adhatoda vasica. J Indian Chem Soc 1:315Google Scholar
  62. Sharrna SD, Gupta VK, Goswami KN, Padmanabhan VM (1993) Crystal structure of deoxy vasicine zinc complex. Cryst Res Technol 28:1115CrossRefGoogle Scholar
  63. Shrivastava N, Shrivastava A, Banerjee A, Nivsakar M (2006) Anti-ulcer activity of Adhatoda vasica Nees. J Herb Pharmacother 6:43–49PubMedGoogle Scholar
  64. Southwick PL, Casanova L (1958) A new synthesis of dl-vasicine and a methoxy analog. J Am Chem Soc 80:1168–1173CrossRefGoogle Scholar
  65. Spath E, Nikawitz E (1934) Die Konstitution des Peganins. Eur J Inorg Chem 67:45Google Scholar
  66. Spath E, Platzer N (1935) Über Derivate des Peganins und ihre Ring-Homologen (VIII. Mitteil. Über Peganin). Eur J Inorg Chem 68:2221Google Scholar
  67. Spath E, Ruffner F (1938) Über das Pyracridon (= α-Chinochinolon) (XIV. Mitteil. über Peganin). Eur J Inorg Chem 71:1657Google Scholar
  68. Spath E, Kuffner F, Platzer N (1935) Synthese und Konstitution des Peganins (Vasicins). Eur J Inorg Chem 68:699–702Google Scholar
  69. Srinivasarao D, Jayaraj IA, Jayaraj R, Prabha ML (2006) A study on antioxidant and anti-inflammatory activity of vasicine against lung damage in rats. Indian J Allergy Asthma 20:1–7Google Scholar
  70. Tothill A (1967) Investigation of adrenaline reversal in the rat uterus by the induction of resistance to isoprenaline. Br J Pharmacol 29:291Google Scholar
  71. Wakhloo RL, Wakhloo D, Gupta OP, Atal CK (1979) Vasicine hydrochloride: a new drug for interruption of pregnancy. J Obstet Gynaecol India 29:939Google Scholar
  72. Wasserman HH, Kuo GH (1991) The chemistry of vicinal tricarbonyls. An efficient synthesis of (±)-vasicine. Tetrahedron Lett 32:7131–7132CrossRefGoogle Scholar
  73. Wu X, Qin G, Cheung KK, Cheng KF (1997) New alkaloids from Isatis indigotica. Tetrahedron 53:13323–13328CrossRefGoogle Scholar
  74. Zabir A, Bhagat A, Gupta OP, Singh GD, Youssouf MS, Dhar KL, Suri OP, Suri KA, Satti NK, Gupta BD, Qazi GN (2006) Synthesis and bronchodilator activity of new quinazolin derivative. Eur J Med Chem 41:429–434CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Kunal Nepali
    • 1
  • Sahil Sharma
    • 1
  • Ritu Ojha
    • 1
  • Kanaya Lal Dhar
    • 2
  1. 1.Department of Pharmaceutical SciencesGuru Nanak Dev UniversityAmritsarPunjab
  2. 2.Laboratory for Drug Design and Synthesis, Department of Pharmaceutical ChemistryIndo-Soviet Friendship (ISF) College of PharmacyMogaIndia

Personalised recommendations