Isolation, Synthesis, and Biological Activity of Quindoline, a Valuable­ Indoloquinoline Natural Product and Useful Key Intermediate­

Abstract

Quindoline is one of the simplest naturally occurring monomeric indoloquinoline alkaloids. Chemists exhibited interest in this compound before it was isolated from a natural source. The different approaches toward the total synthesis of the natural product and its performance in various biological tests are discussed. Aspects related to the isolation of quindoline from different ethnomedicinally relevant plants around the world are also reviewed.

1 Introduction

2 Isolation and Biogenetic Considerations

3 Total Syntheses of Quindoline

3.1 Early Synthetic Studies

3.2 Syntheses from Benzenoids

3.3 Syntheses from Indoles

3.4 Syntheses from Quinolines

4 Biological Activity Studies

5 Conclusions

Key words

quindoline - heterocyclic natural products - chemical synthesis - indoloquinolines - bioactive alkaloids - synthetic approaches

• References

• 1a Nakanishi K. A Brief History of Natural Products Chemistry . In Comprehensive Natural Products Chemistry . Vol. 1. Barton DH. R. Nakanishi K. Meth-Cohn O. Elsevier; Amsterdam: 1999: 1-31
• 1b Ji H.-F. Li X.-J. Zhang H.-Y. EMBO Rep. 2009; 10: 194
• 2a Ekor M. Front. Pharmacol. 2013; DOI: org/10.3389/fphar.2013.00177
• 2b Dias DA. Urban S. Roessner U. Metabolites 2012; 2: 303 ; http://www.mdpi.com/journal/metabolites
• 2c Plant Bioactives and Drug Discovery: Principles, Practice, and Perspectives. Cechinel JrV. Wiley; New York: 2012
• 3a Wetzel S. Lachance H. Waldmann H. Natural Products as Lead Sources for Drug Development . In Comprehensive Natural Products II: Chemistry and Biology . Vol. 3. Liu H.-W. Mander L. Elsevier; Amsterdam: 2010: 5-45
• 3b Rodrigues T. Reker D. Schneider P. Schneider G. Nat. Chem. 2016; 8: 531
• 3c Cragg GM. Newman DJ. Biochim. Biophys. Acta 2013; 1830: 3670
• 3d Newman DJ. Cragg GM. J. Nat. Prod. 2007; 70: 461
• 3e Hong J. Chem.–Eur. J. 2014; 20: 10204
• 4a Alkaloids: A Treasury of Poisons and Medicines . Funayama S. Cordell GA. Academic Press; New York: 2014
• 4b Hamid HA. Ramli AN. M. Yusoff MM. Front. Pharmacol. 2017;
• 4c Amirkia V. Heinrich M. Phytochem. Lett. 2014; 10: 48
• 4d Kuramoto M. Arimoto H. Uemura D. Mar. Drugs 2004; 2: 39 ; http://www.mdpi.com/journal/marinedrugs
• 4e Cushnie TP. T. Cushnie B. Lamb AJ. Int. J. Antimicrob. Agents 2014; 44: 377
• 4f Rishton GM. Am. J. Cardiol. 2008; 101: 43D
• 5 Kaufman TS. Rúveda EA. Angew. Chem. Int. Ed. 2005; 44: 854
• 6 Parvatkar PT. Parameswaran PS. Curr. Org. Synth. 2016; 13: 58
• 7a Hostyn S. Maes BU. W. Pieters L. Lemière GL. F. Mátyus P. Hajós G. Dommisse R. Tetrahedron 2005; 61: 1571
• 7b Dhanabal T. Sangeetha R. Mohan PS. Tetrahedron 2006; 62: 6258
• 8 Dwuma-Badu D. Ayim JS. K. Fiagbe NY. Y. Knapp JE. Schiff PL. Jr. Slatkin DJ. J. Pharm. Sci. 1978; 67: 433
• 9 Subbaraju GV. Kavitha J. Rajasekhar D. Jimenez JI. J. Nat. Prod. 2004; 67: 461
• 10 Crouch RC. Davis AO. Spitzer TD. Martin GE. Sharaf MH. M. Schiff PL. Jr. Phoebe CH. Tackie AN. J. Heterocycl. Chem. 1995; 32: 1077
• 11 Sharaf MH. M. Schiff PL. Jr. Tackie AN. Phoebe CH. Jr. Martin GE. J. Heterocycl. Chem. 1996; 33: 239
• 12 Pousset J.-L. Martin M.-T. Jossang A. Bodo B. Phytochemistry 1995; 39: 735
• 13a Ablordeppey SY. Hufford CD. Borne RF. Dwama-Badu D. Planta Med. 1990; 56: 416
• 13b Tackie AN. Sharaf MH. M. Schiff PL. Jr. Boye GL. Crouch RC. Martin GE. J. Heterocycl. Chem. 1991; 28: 1429
• 14a Hadden CE. Sharaf MH. M. Guido JE. Robins RH. Tackie AN. Phoebe CH. Jr. Schiff PL. Jr. Martin GE. J. Nat. Prod. 1999; 62: 238
• 14b Fort DM. Litvak J. Chen JL. Lu Q. Phuan PW. Cooper R. Bierer DE. J. Nat. Prod. 1998; 61: 1528
• 15 Paulo A. Gomes ET. Houghton PJ. J. Nat. Prod. 1995; 58: 1485
• 16a Sharaf MH. M. Schiff PL. Jr. Tackie AN. Phoebe CH. Jr. Howard L. Myers C. Hadden CE. Wrenn SK. Davis AO. Andrews CW. Minick D. Johnson RL. Shockcor JP. Crouch RC. Martin GE. Magn. Reson. Chem. 1995; 33: 767
• 16b Tackie AN. Boye GL. Sharaf MH. M. Schiff PL. Jr. Crouch RC. Spitzer TD. Johnson RL. Dunn J. Minick D. Martin GE. J. Nat. Prod. 1993; 56: 653
• 16c Blinov K. Elyashberg M. Martirosian R. Molodtsov SG. Williams AJ. Tackie AN. Sharaf MH. M. Schiff PL. Jr. Crouch RC. Martin GE. Hadden CE. Guido JE. Mills KA. Magn. Reson. Chem. 2003; 41: 577
• 16d Cimanga K. de Bruyne T. Pieters L. Claeys M. Vlietnick A. Tetrahedron Lett. 1996; 37: 1703
• 17a Larghi EL. Bracca AB. J. Arroyo Aguilar AA. Heredia DA. Pergomet JL. Simonetti SO. Kaufman TS. Curr. Top. Med. Chem. 2015; 17: 1683
• 17b Parvatkar PT. Tilve SG. Bioactivities and Synthesis of Indoloquinoline Alkaloids: Cryptolepine, Isocryptolepine and Neocryptolepine. In Bioactive Heterocycles: Synthesis and Biological Evaluation. Ameta KL. Pawar RP. Domb AJ. Nova Science Publishers; New York: 2013. Chap. 10, 217–23
• 17c Kumar EV. K. S. Etukala JR. Ablordeppey SY. Mini-Rev. Med. Chem. 2008; 8: 538
• 17d Wright CW. J. Pharm. Pharmacol. 2007; 59: 899
• 18 Oyekan AO. Ablordeppey SY. Med. Chem. Res. 1996; 6: 602
• 19a Ansah C. Mensah KB. Ghana Med. J. 2013; 47: 137
• 19b Pal HC. Prasad R. Katiyar SK. Sci. Rep. 2017; 7
• 19c Pal HC. Prasad R. Katiyar SK. Molecules 2016; 21: 1758 ; DOI:10.3390/molecules21121758
• 19d Olajide OA. Bhatia HS. de Oliveira AC. Wright CW. Fiebich BL. Eur. J. Med. Chem. 2013; 63: 333
• 20a Shen FH. Jin J. Li J. Wang Y. Zhu SH. Lu YJ. Ou TM. Huang ZS. Huang M. Huang ZY. Pharm. Biol. 2013; 51: 447
• 20b Ou TM. Lu Y.-J. Zhang C. Huang Z.-S. Wang X.-D. Tan J.-H. Chen Y. Ma D.-L. Wong K.-Y. Tang JC.-O. Chan AS.-C. Gu L.-Q. J. Med. Chem. 2007; 50: 1465
• 20c Lu YJ. Ou TM. Tan JH. Hou JQ. Shao WY. Peng D. Sun N. Wang XD. Wu WB. Bu XZ. Huang ZS. Ma DL. Wong KY. Gu LQ. J. Med. Chem. 2008; 51: 6381
• 20d Jana J. Mondal S. Bhattacharjee P. Sengupta P. Roychowdhury T. Saha P. Kundu P. Chatterjee S. Sci. Rep. 2017; 7 : article number 40706; doi:10.1038/srep40706
• 20e Ghosh S. Jana J. Kar RK. Chatterjee S. Dasgupta D. Biochemistry 2015; 54: 974
• 20f Chen J. Deady LW. Kaye AJ. Finlay GJ. Baguley BC. Denny WA. Bioorg. Med. Chem. 2002; 10: 2381
• 20g Zhao M. Kamada T. Takeuchi A. Nishioka H. Kuroda T. Takeuchi Y. Bioorg. Med. Chem. Lett. 2015; 25: 5551
• 20h Yin R. Zhang M. Hao C. Wang W. Qiu P. Wan S. Zhang L. Jiang T. Chem. Commun. 2013; 49: 8516
• 21 Spitzer TD. Crouch RC. Martin GE. Sharaf MH. M. Schiff PL. Jr. Tackie AN. Gilbert LB. J. Heterocycl. Chem. 1991; 28: 2065
• 22a Sharaf MH. M. Schiff PL. Jr. Tackie AN. Phoebe CH. Jr. Johnson RL. Minick D. Andrews CW. Crouch RC. Martin GE. J. Heterocycl. Chem. 1996; 33: 789
• 22b Paulo A. Gomes ET. Steele J. Warhurst DC. Houghton PJ. Planta Med. 2000; 66: 30
• 23 Hutchinson J. Dalziel JM. Flora of Tropical West Africa . The Whitefrairs Press; London: 1963: 102
• 24a Oliver-Bever B. Medicinal Plants in Tropical West Africa . University Press; Cambridge: 1986
• 24b Kerharo J. La Pharmacopée Sénégalaise Traditionnelle, Plantes Médicinales et Toxiques. Editions Vigot Frères; Paris: 1974
• 24c Watt JM. Breyer-Brandwijk MG. The Medicinal and Poisonous Plants of Southern and Eastern Africa . E. & S. Livingstone; London: 1962
• 24d Cimanga K. de Bruyne T. Lasure A. Van Poel B. Pieters L. Claeys M. Vanden Berghe D. Kambu K. Tona L. Vlietinck AJ. Planta Med. 1996; 62: 22
• 24e Iwu M. Handbook of African Medicinal Plants . CRC Press; Boca Raton: 1993
• 25a Bandeira S. Bolnick D. Barbosa F. Wild Flowers of Southern Mozambique . Universidade Eduardo Mondlane; Maputo / Mozambique: 2007. 195
• 25b Darbyshire I. Vollesen K. Kelbessa E. Acanthaceae (Part 2) Flora of Tropical East Africa . Royal Botanic Gardens; Kew UK: 2010: 548-550
• 26a Adia MM. Anywar G. Byamukama R. Kamatenesi-Mugisha M. Sekagya Y. Kakudidi EK. Kiremire BT. J. Ethnopharmacol. 2014; 155: 580
• 26b Stangeland T. Alele PE. Katuura E. Lye KA. J. Ethnopharmacol. 2011; 137: 154
• 27 Calderón AI. Hodel A. Wolfender J.-L. Gupta MP. Correa M. Hostettmann K. Nat. Prod. Res. 2013; 27: 1335
• 28a Kone WM. Koffi AG. Bomisso EL. Bi FH. T. Afr. J. Tradit., Complementary Altern. Med. 2012; 9: 81
• 28b N’guessan K. Kouassi KH. Ouattara D. J. Appl. Sci. Res. 2010; 6: 1291
• 29a Manda P. Abrogoua DP. Bahi C. Dano DS. Gnahoui G. Kablan BJ. Afr. J. Pharm. Pharmacol. 2011; 5: 1838
• 29b N’guessan K. Soro D. Amon AD. E. Phytothérapie 2011; 9: 199
• 30a Schnee L. Plantas Comunes de Venezuela . Ediciones de la biblioteca de Universidad Central de Venezuela; Caracas Venezuela: 1984: 413
• 30b Mahabir D. Gulliford MC. Pan Am. J. Public Health 1997; 1: 174
• 30c Wong W. Econ. Bot. 1976; 30: 103
• 31 Chaves OS. Teles YC. F. de Oliveira Monteiro MM. Mendes LG. Jr. de Fátima Agra M. de Andrade Braga V. Silva TM. S. de Souza MF. V. Molecules 2017; 22: 94 ; DOI: 10.3390/molecules22010094
• 32a Neuwinger HD. African Traditional Medicine: A Dictionary of Plant Use and Applications . Medpharm Scientific; Stuttgart: 2000
• 32b Perumal B. Sida L. . In Plant Resources of South-East Asia No 12(2): Medicinal and Poisonous Plants . Vol. 2. van Valkenburg JL. C. H. Bunyapraphatsara N. Backhuys Publishers; Leiden: 2001: 496
• 32c Dinda B. Das N. Dinda S. Dinda M. Silsharma I. J. Ethnopharmacol. 2015; 176: 135
• 33a Plant Pigments and their Manipulation . In Annual Plant Reviews . Vol. 14. Davies KM. Wiley-Blackwell; New York: 2004
• 33b Zook M. Plant Physiol. 1998; 118: 1389
• 33c Medvedev AE. Clow A. Sandler M. Glover V. Biochem. Pharmacol. 1996; 52: 385
• 33d Gu J.-D. Berry DF. Appl. Environ. Microbiol. 1991; 57: 2622
• 34 Valli G. Vinnarasi J. Int. J. Pure Appl. Chem. 2011; 6: 273
• 35a Fichter F. Boehringer R. Chem. Ber. 1906; 39: 3932
• 35b Schützenberger MP. C. R. Hebd. Seances Acad. Sci. 1877; 85: 147
• 36a Giraud ME. C. R. Hebd. Seances Acad. Sci. 1879; 89: 104
• 36b Giraud ME. C. R. Hebd. Seances Acad. Sci. 1880; 90: 1429
• 36c Armit J. Robinson J. J. Chem. Soc., Trans. 1922; 121: 827
• 37 Fichter F. Rohner F. Chem. Ber. 1910; 43: 3489
• 38a Yamabe S. Tsuchida N. Yamazaki S. J. Org. Chem. 2006; 71: 1777
• 38b Xiao M. Wu W. Wei L. Jin X. Yao X. Xie Z. Tetrahedron 2015; 71: 3705
• 38c Burke AJ. Marques CS. Mini-Rev. Org. Chem. 2007; 4: 310
• 39 Montoya Sánchez N. de Klerk A. Energy Fuels 2015; 29: 7910
• 40 Holt SJ. Petrow V. J. Chem. Soc. 1947; 607
• 41a Clemo GR. Felton DG. I. J. Chem. Soc. 1952; 1652
• 41b Gellért E. Raymond-Hamet Schlittler E. Helv. Chim. Acta 1951; 34: 642
• 42 Bracca AB. J. Heredia DA. Larghi EL. Kaufman TS. Eur. J. Org. Chem. 2014; 7979
• 43 Rádl S. Konvička P. Váchal P. J. Heterocycl. Chem. 2000; 37: 855
• 44 Ho T.-L. Jou D.-G. Helv. Chim. Acta 2002; 85: 3823
• 45 Bhandari S. Ray S. Synth. Commun. 1998; 28: 765
• 46a Dutta B. Jayanta SS. Ray JK. Tetrahedron Lett. 2006; 47: 377
• 46b Ziegenbein W. Franke W. Angew. Chem. 1959; 71: 573
• 47 Söderberg BC. G. Curr. Org. Chem. 2000; 4: 727
• 48a Sharples D. Hajos G. Riedl Z. Csnyi D. Molnr J. Szabo D. Arch. Pharm. (Weinheim, Ger.) 2001; 334: 269
• 48b Budén ME. Bardagi JI. Rossi RA. Curr. Org. Synth. 2017; 14: 398
• 49 Mendez M. V., Kaufman T. S., Bracca A. B. J.; unpublished results.
• 50a Zhao J. Wu C. Li P. Ai W. Chen H. Wang C. Larock RC. Shi F. J. Org. Chem. 2011; 76: 6837
• 50b Zhao J. Li P. Wu C. Chen H. Ai W. Sun R. Ren H. Larock RC. Shi F. Org. Biomol. Chem. 2012; 10: 1922
• 50c Reddy YP. Reddy KK. Indian J. Chem., Sect. B 1988; 27: 563
• 51 Lavrado J. Cabal GG. Prudencio M. Mota MM. Gut J. Rosenthal PJ. Diaz C. Guedes RC. Dos Santos DJ. V. A. Bichenkovss E. Douglas KT. Moreira R. Paulo A. J. Med. Chem. 2011; 54: 734
• 52a Gorlitzer K. Weber J. Arch. Pharm. (Weinheim, Ger.) 1981; 314: 850
• 52b Gorlitzer K. Weber J. Arch. Pharm. (Weinheim, Ger.) 1981; 314: 852
• 53a Bierer DE. Dubenko LG. Zhang PS. Lu Q. Imbach PA. Garofalo AW. Phuan PW. Fort DM. Litvak J. Gerber RE. Sloan B. Luo J. Cooper R. Reaven GM. J. Med. Chem. 1998; 41: 2754
• 53b Bierer DE. Fort DM. Mendez CD. Luo J. Imbach PA. Dubenko LG. Jolad SD. Gerber RE. Litvak J. Lu Q. Zhang PS. Reed MJ. Waldeck N. Bruening RC. Noamesi BK. Hector RF. Carlson TJ. King SR. J. Med. Chem. 1998; 41: 894
• 54a Ablordeppey SY. Fan PC. Li SM. Clark AM. Hufford CD. Bioorg. Med. Chem. 2002; 10: 1337
• 54b Cooper MM. Lovell JM. Joule JA. Tetrahedron Lett. 1996; 37: 4283
• 55 Lavrado J. Paulo A. Gut J. Rosenthal PJ. Moreira R. Bioorg. Med. Chem. Lett. 2008; 18: 1378
• 56 Mardenborough LG. Zhu XY. Fan P. Jacob MR. Khan SI. Walker LA. Ablordeppey SY. Bioorg. Med. Chem. 2005; 13: 3955
• 57a Wright CW. Addae-Kyereme J. Breen AG. Brown JE. Cox MF. Croft SL. Goekcek Y. Kendrick H. Phillips RM. Pollet PL. J. Med. Chem. 2001; 44: 3187
• 57b Yang S.-W. Abdel-Kader M. Malone S. Werkhoven MC. M. Wisse JH. Bursuker I. Neddermann K. Fairchild C. Raventos-Suarez C. Menendez AT. Lane K. Kingston DG. I. J. Nat. Prod. 1999; 62: 976
• 58 Lai TK. Chatterjee A. Banerji J. Sarkar D. Chattopadhyay N. Helv. Chim. Acta 2008; 91: 1975
• 59 dos S Bastos D. Silva AC. Albert AL. M. Barros WM. R. Slana GB. C. A. Cardoso JN. Lopes RS. C. Lopes CC. Tetrahedron Lett. 2013; 54: 3144
• 60 Santos RP. Lopes RS. C. Lopes CC. Synthesis 2001; 845
• 61 Smith MB. In March’s Advanced Organic Chemistry: Reactions, Mechanism, and Structure . March J. Wiley; New Jersey: 2007
• 62 Fan P. Ablordeppey SY. J. Heterocycl. Chem. 1997; 34: 1789
• 63 Ablordeppey SY. Fan P. Clark AM. Nimrod A. Bioorg. Med. Chem. 1999; 7: 343
• 64 Etukala JR. Suresh Kumar EV. K. Ablordeppey SY. J. Heterocycl. Chem. 2008; 45: 507
• 65 Arzel E. Rocca P. Marsais F. Godard A. Quéguiner G. Tetrahedron Lett. 1998; 39: 6465
• 66 Csányi D. Timári G. Hajós G. Synth. Commun. 1999; 29: 3959
• 67 Wippich J. Truchan N. Bach T. Adv. Synth. Catal. 2016; 358: 2083

For recent examples, see:
• 68a Kim JY. Park SH. Ryu J. Cho SH. Kim SH. Chang S. J. Am. Chem. Soc. 2012; 134: 9110
• 68b Thirunavukkarasu VS. Raghuvanshi K. Ackermann L. Org. Lett. 2013; 15: 3286
• 68c Lee D. Kim Y. Chang S. J. Org. Chem. 2013; 78: 11102
• 68d Kim J. Kim J. Chang S. Chem.–Eur. J. 2013; 19: 7328
• 68e Shin K. Ryu J. Chang S. Org. Lett. 2014; 16: 2022
• 68f Peng J. Xie Z. Chen M. Wang J. Zhu Q. Org. Lett. 2014; 16: 4702
• 68g Zhang L.-L. Li L.-H. Wang Y.-Q. Yang Y.-F. Liu X.-Y. Liang Y.-M. Organometallics 2014; 33: 1905
• 68h Park SH. Kwak J. Shin K. Ryu J. Park Y. Chang S. J. Am. Chem. Soc. 2014; 136: 2492
• 69 Guo R.-N. Cai X.-F. Shi L. Chen Z.-P. Zhou Y.-G. Chem.–Eur. J. 2014; 20: 8343
• 70 Arzel E. Rocca P. Grellier P. Labaeid M. Frappier F. Gueritte F. Gaspard C. Marsais F. Godard A. Quéguiner G. J. Med. Chem. 2001; 44: 949
• 71 Hostyn S. Maes BU. W. Van Baelen G. Gulevskaya A. Meyers C. Smits K. Tetrahedron 2006; 62: 4676

For some examples, see:
• 72a Jonckers TH. M. Maes BU. W. Lemière GL. F. Rombouts G. Pieters L. Haemers A. Dommisse RA. Synlett 2003; 615
• 72b Ferreira IC. F. R. Queiroz M.-JR. P. Kirsch G. Tetrahedron 2003; 59: 3737
• 72c Dajka-Halász B. Monsieurs K. Eliás O. Károlyházy L. Tapolcsányi P. Maes BU. W. Riedl Z. Hajós G. Dommisse RA. Lemière GL. F. Kosmrlj J. Mátyus P. Tetrahedron 2004; 60: 2283
• 72d Mátyus P. Maes BU. W. Riedl Z. Hajós G. Lemière GL. F. Tapolcsányi P. Monsieurs K. Eliás O. Dommisse RA. Krajsovszky G. Synlett 2004; 1123
• 73 Bogányi B. Kámán J. Tetrahedron 2013; 69: 9512
• 74 Bogányi B. Kámán J. J. Heterocycl. Chem. 2009; 46: 33
• 75 Letessier J. Detert H. Synthesis 2012; 44: 290

For some examples, see:
• 76a Merritt EA. Malmgren J. Klinke FJ. Olofsson B. Synlett 2009; 2277
• 76b Bielawski M. Olofsson B. Kraemer K. Lautens M. Org. Synth. 2009; 86: 308
• 76c Zhu M. Jalalian N. Olofsson B. Synlett 2008; 592
• 76d Bielawski M. Olofsson B. Chem. Commun. 2007; 2521
• 76e Bielawski M. Zhu M. Olofsson B. Adv. Synth. Catal. 2007; 349: 2610
• 76f Letessier J. Detert H. Schollmeyer D. Acta Crystallogr., Sect. E 2011; E67: o2494
• 77 Sharma KS. Kumari S. Singh RP. Synthesis 1981; 316
• 78 Tagata T. Nishida M. J. Org. Chem. 2003; 68: 9412
• 79 Krasnokutskaya EA. Semenischeva NI. Filimonov VD. Knochel P. Synthesis 2007; 81
• 80 Haddach AA. Kelleman A. Deaton-Rewolinski MV. Tetrahedron Lett. 2002; 43: 399
• 81 Boahen YO. Mann J. Chem. Nat. Compd. 2014; 50: 494
• 82 Caprio V. Guyen B. Opoku-Boahen Y. Mann J. Gowan SM. Kelland LM. Read MA. Neidle S. Bioorg. Med. Chem. Lett. 2000; 10: 2063
• 83 Wentrup C. Lan NM. Lukosch A. Bednarek P. Kvaskoff D. Beilstein J. Org. Chem. 2013; 9: 743
• 84 Styczynski P. US 20030012755, 2003