Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Synthesis and In Vitro Evaluation of Some Novel Benzofuran Derivatives as Potential Anti-HIV-1, Anticancer, and Antimicrobial Agents

  • Rida, Samia M. (Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Alexandria) ;
  • EI-Hawash, Soad A.M. (Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Alexandria) ;
  • Fahmy, Hesham T.Y. (Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University) ;
  • Hazza, Aly A. (Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Alexandria) ;
  • EI-Meligy, Mostafa M.M. (Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Alexandria)
  • Published : 2006.01.01
Download PDF
⟨ Previous Next ⟩

Abstract

A novel series of 1-(1-benzofuran-2-yl-ethylidene)-4-substituted thiosemicarbazides (2a-d) along with some derived ring systems: substituted-2,3-dihydro-thiazoles(3a-c, 4a-f) and thiazolidin-4-ones(5a-d and 6a-d), were synthesized. In addition, cyanoacetic acid-(1-benzofuran-2-yl-ethylidene) hydrazide(7) was used to prepare another new series of compounds consisting of substituted pyridin-2(1H)-ones(8a-c); 2-thioxo-2,3-dihydro-thiazoles(9a-d) and 2-thioxo-2,3-dihydro-6H-thiazolo[4,5-d]pyrimidin-7-ones (10a-c, 11a-c). The absolute configuration of compound 5c was determined by X-ray crystallography. The compounds prepared were evaluated for their in vitro anti-HIV, anticancer, antibacterial, and antifungal activities. Among the tested compounds, compounds 5c and 9a produced a significant reduction ㅐ ㄹ the viral cytopathic effect (93.19% and 59.55%) at concentrations $>2.0{\times}10^{-4}\;M\;and\;2.5{\times}10^{-5}\;M$respectively. Compound 9a was confirmed to have moderate anti-HIV activity. Compounds 2a, 2d, and 5c showed mild antifungal activity. However, none of the tested compounds showed any significant anticancer activity.

Keywords

References

  1. Altomar, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M.C., Polidori, G., and Camalli, M., J. Appl. Cryst., 27, 435 (1994)
  2. Badawey, E. A. M., Hazzaa, A. A., Rida, S. M., and Fahmy, H. T. Y., Assessment of anti-HIV activity of some benzimidazolylthiazoles. Arch. Pharm.(Weinheim), 325, 565-567 (1992) https://doi.org/10.1002/ardp.19923250908
  3. Bekhit, A. A., Fahmy, H. T., Rostom, S. A., and Beraka, A. M., Design and synthesis of some substituted 1H-pyrazolylthiazolo[4,5-d]pyrimidines as anti-inflammatory-antimicrobial agents. Eur. J. Med. Chem., 38, 27-36 (2003) https://doi.org/10.1016/S0223-5234(02)00009-0
  4. Conte, J. E. and Barriere, S. L., Manual of Antibiotics and Infectious Diseases, 1st Ed. Lea and Febiger, U.S.A., 135 (1988)
  5. Fahmy, H. T., Rostom, S. A., Saudi, M. N., Zjawiony, J. K., and Robins, D. J., Synthesis and in vitro evaluation of the anticancer activity of novel fluorinated thiazolo[4,5-d]pyrimidines. Arch. Pharm. Pharm. Med. Chem., 336, 216-225 (2003) https://doi.org/10.1002/ardp.200300734
  6. Fahmy, H. T., Rostom, S. A., and Bekit, A. A., Synthesis and antitumor evaluationof new poly substituted thiazole and derived thiazolo[4,5-d]pyrimidine systems. Arch. Pharm. Pharm. Med. Chem., 335, 213-222 (2002) https://doi.org/10.1002/1521-4184(200205)335:5<213::AID-ARDP213>3.0.CO;2-H
  7. Grever, M., Schepartz, S., and Chabner, B., The National Cancer Institute Cancer Drug Discovery and Development Program Semin. Oncol., 19, 622 (1992)
  8. Hoffman, J. M., Smith, A. M., Rooney, C. S., Fisher, T. E., and Wai, J. S., Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. J. Med. Chem., 36, 953-966 (1993) https://doi.org/10.1021/jm00060a002
  9. Holla, B. S., Rao, B. S., Sarojini, B. K., and Akberali, P. M., One pot synthesis of thiazoldihydropyrimidinones and evaluation of their anticancer activity. Eur. J. Med. Chem., 39, 777-783 (2004) https://doi.org/10.1016/j.ejmech.2004.06.001
  10. James, L. T., Carly, A. P., Erik, C. M., Heather, L. H., Stephen, J. H., Richard, B. H., Phillip Bowen, J., Konstantinos, K., John, A. H., and Moses Lee, Sequence selective recognition of DNA by hairpin conjugates of a racemic seco-cyclopropaneindoline- 2-benzofurancarboxamide and polyamides. Bioorg. Med. Chem., 12, 2245-2248 (2002) https://doi.org/10.1016/S0960-894X(02)00341-4
  11. Kawasaki, K., Masubuchi, M., Morikami, K., Sogabi, S., Aoyama, Ebiike, H., Niizuma, S., Hayase, M, Fujii, T., Sakata, K., Sindoh, H., Shiratori, Y., Aoki, Y., Ohtsuka, T., and Shimma, N., Design and synthesis of novel benzofurans as antifungal agents targeting fugal N-myristoyltransferase. Part 3. Bioorg. Med. Chem. Lett., 13, 87-91 (2003) https://doi.org/10.1016/S0960-894X(02)00844-2
  12. Kini, G. D., Anderson, J. D., Sanghvi, Y. S., Lewis, A. F., Smee, D. F., Revankar, G. R., Robins, R. K., and Cottam, H. B., Synthesis and antiviral activity of Certain guanosine analogues in the thiazolo [4,5-d]pyrimidine ring system. J. Med. Chem., 34, 3006-3010 (1991) https://doi.org/10.1021/jm00114a008
  13. Koka, M., Sevi, S., Kirilmis, C., Kazaz, C., Ozbek, B., and Otuk, G., Synthesis and antimicrobial activity of some novel derivatives of benzofuran: Part 1. Synthesis and antimicrobial activity of Benzofuran-2-yl-(3-phenyl-3-methylcyclobutyl)- ketoxime derivatives. Eur. J. Med. Chem, 40, 1351-1358 (2005) https://doi.org/10.1016/j.ejmech.2005.07.004
  14. Nagahara, K., Anderson, J. D., Kini, G. D., Dalley, N. K., Larson, S. B., Smee, D. F., Jin, A., Sharma, B. S., Jolley, W. B., Robins, R. K. et al., Thiazolo 4[,5-d]pyrimidine nucleosides. The synthesis of certain 3-beta-D-ribo furanosylthiazolo [4,5- d]pyrimidines as potential immunotherapeutic agents. J. Med. Chem., 33, 407-415(1990) https://doi.org/10.1021/jm00163a064
  15. Rida, S. M., Habib, N. S., Badawey, E. A. M., Fahmy, H. T. Y., and Ghozlan, H. A., Synthesis and biological investigation of some New thiazolylbenzimidazoles and benzimidazolylthiazolo[ 3,2-a]pyrimidines. Arch. Pharm.(Weinheim), 328, 325-328 (1995) https://doi.org/10.1002/ardp.19953280406
  16. Romero, D., Thomas, R., May, P., and Poel, T., Anti-AIDS heteroaryl-substituted piperazines, aminopiperidines and peperidines, US Appl., 354,925, 13 Dec. (1994)
  17. Romero, D., Thomas, R., May, P., and Poel, T., Anti-AIDS heteroaryl-substituted piperazines, aminopiperidines and peperidines, Chem. Abstr., 125, 142777g (1996)
  18. Said, M., Abouzid, K., Mouneer, A., Ahmedy, A., Osman, A. M., Synthesis and biological evaluation of new thiazolopyrimidines. Arch. Pharm. Res., 27, 471-477 (2004) https://doi.org/10.1007/BF02980118
  19. Scott, A. C., Laboratory Control of Antimicrobial Therapy. In: Colle, J. G., Duguid, J. P., Fraser, A. G., Marmion, B. P., Mackie and MacCartney Practical Medical Microbiology, Churchil Livingstone, 13th edition, 2, 161-181 (1989)
  20. Vacca, J., Lin, J., Yeh, K., Chodakewitz, J., Deutsch, P., and Ju, W., Combination therapy for the treatment of AIDS, US Appl., 19,590 (1998)
  21. Vacca, J., Lin, J., Yeh, K., Chodakewitz, J., Deutsch, P., and Ju, W., Combination therapy for the treatment of AIDS, Chem. Abstr., 131, 690y (1999)
  22. Varvaresou, A., Iakovou, K., Filippatos, E., Souli, C., Calogeropoulou, T., Ioannidou, I., Kourounakis, A. P., Pannecouque, C., Witvrouw, M., Padalko, E.; Neyts, J., De Clercq, E., and Tsotinis, A., Synthesis, Anti-retroviral and antioxidant evaluation of a series of new benzo[b]furan derivatives. Arzneim. Forch., 51, 156-162 (2001)
  23. Villere, G. and Grinsteins, V., Latvijas Valsts Univ. Kim. Fak. Zinatniskie Raksti, 22, 129-35 (1958)
  24. Vinh, T. K., Yee, S. W., Kirby, A. J., Nicholls, P. J., and Simons, C., 1-[(Benzofuran-2-yl)phenylmethyl]triazoles as steroidogenic inhibitors: Synthsis and in vitro inhibition of human placental CYP19 aromatase. Anticancer Drug Res., 16, 217- 225 (2001)
  25. Wahab Khan, M., Jahangir Alam, M., Rashid, M., and Chowdhury, R., A new structural alternative in benzo[b]furans for antimicrobial activity. Bioorg. Med. Chem., 13, 4796-4805 (2005) https://doi.org/10.1016/j.bmc.2005.05.009
  26. Wang, Y., Yuan, H., Ye, W., Wright, S., Wang, H., and Larrick, J., Synthesis and preliminary biological evaluation of CC- 1065 Analogues: Effects of different linkers and terminal amides on biological activity. J. Med. Chem., 43, 1541-1549 (2000) https://doi.org/10.1021/jm990514c
  27. Weislow, O. S., Kiser, R., Fine, D. L., Bader, J., Shoemaker, R. H., and Boyd, M. R., New soluble-formazan assay for HIV-1 cytopathic effects : application to high-fulx screening of synthetic and natural products for AIDS-antiviral activity. J. Natl. Cancer Inst., 81, 577-586 (1989) https://doi.org/10.1093/jnci/81.8.577
  28. Whomsley, R., Fernandez, E., Nicholls, P. J., Smith, H. J., Lombardi, P., and Pestellini, V., Substituted 1-[(Benzofuran- 2-yl)phenylmethyl]imidazoles as potent inhibitors of aromatase in vitro and female rats in vivo. J. Steroid Biochem. Mol. Biol., 44, 675-676 (1993) https://doi.org/10.1016/0960-0760(93)90279-6