Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2653–2665 | Cite as

Synthesis, crystal structure, anti-HIV, and antiproliferative activity of new pyrazolylthiazole derivatives

  • Murtaza Madni
  • Shahid Hameed
  • Muhammad N. Ahmed
  • Muhammad N. Tahir
  • Najim A. Al-Masoudi
  • Christophe Pannecouque
Original Research

Abstract

The development of new HIV-1 non-nucleoside reverse transcriptase inhibitors offers the possibility of generating novel structures of increased potency. Based on the bioisosteric principle, new series of N′-benzylidene-2-(5-(4-chlorophenyl)-3-phenyl-4,5-dihydropyrazol-1-yl)thiazole-4-carbohydrazide schiff bases 5ax containing 1,3-thiazole clubbed with 2-pyrazoline was synthesized and characterized by spectroscopic techniques. The structure of the synthesized compounds was unambiguously confirmed by single-crystal X-ray diffraction analysis of compound 5k. All the new analogs were evaluated in vitro for antiviral activity against the replication of HIV-1 and HIV-2 in MT4 cells using MTT assay. The results showed that only compounds 5n, and 5r possess potent activity against HIV-1 replication (IC50 = 0.50, 0.45 μM, SI = 3 and 5), respectively. None of the compounds are active against HIV-2. Furthermore, compounds 5a, 5i, 5n, and 5r were evaluated for their antiproliferative activity against two solid tumor-derived cell lines consisting MCF-7 (breast cancer) and Hep-G2 (human hepatocarcinoma).

Keywords

Anti-HIV activity Antiproliferative activity Crystal structure NNRTIs 1,3-Thiazole Pyrazole 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

References

  1. Akhtar T, Hameed S, Al-Masoudi NA, Loddo R, La Colla P (2008) In vitro antitumor and antiviral activities of new benzothiazole and 1,3,4-oxadiazole-2-thione. Acta Pharm 58:135–149CrossRefPubMedGoogle Scholar
  2. Ali MA, Yar MS, Siddiqui AA, Sriram D, Yogeeswari P, De Clercq E (2007) Synthesis and anti-HIV activity of N1-nicotinoyl-3-(4′-hydroxy-3′-methylphenyl)-5-[substituted phenyl]-2-pyrazolines. Acta Pol Pharm 63:423–428Google Scholar
  3. Ali I, Wani WA, Khan A, Haque A, Ahmad A, Saleem K, Manzoor N (2012) Synthesis and synergistic antifungal activities of a pyrazoline based ligand and its copper(II) and nickel(II) complexes with conventional antifungals. Microb Pathog 53:66–73CrossRefPubMedGoogle Scholar
  4. Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, Abbott BJ, Mayo LG, Schoemaker RH, Boyd MR (1988) Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 48:589–601PubMedGoogle Scholar
  5. Al-Soud YA, Al-Sa’doni HH, Sabera SOW, Al-Shaneek RHM, Al-Masoudi NA, Loddo R, La Colla P (2010) Synthesis, in vitro antiproliferative and anti-HIV activity of new derivatives of 2-piperazino-1,3-benzo[d]thiazoles. Z Naturforsch 65b:1372–1380Google Scholar
  6. Antonelli G, Turriziani O (2012) Antiviral therapy: old and current issues. Int J Antimicrob Agents 40:95–102CrossRefPubMedGoogle Scholar
  7. Asahchop EL, Wainberg MA, Sloan RD, Tremblay CL (2012) Antiviral drug resistance and the need for development of new HIV-1 reverse transcriptase inhibitors. Antimicrob Agents Chemother 56:5000–5008CrossRefPubMedPubMedCentralGoogle Scholar
  8. Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L (1993) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–871CrossRefGoogle Scholar
  9. Bell FW, Cantrell AS, Hoegberg M, Jaskunas SR, Johansson NG, Jordan CL, Kinnick MD, Lind P, Morin Jr JM, Noreen R, Oberg B, Palkowitz JA, Parrish CA, Pranc P, Sahlberg C, Ternansky RJ, Vasileff RT, Vrang L, West SJ, Zhang H, Zhou X-X (1995) Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure–activity relationship studies of PETT analogs. J Med Chem 38:4929–4936CrossRefPubMedGoogle Scholar
  10. Bhandari S, Tripathi AC, Saraf SK (2013) Novel 2-pyrazoline derivatives as potential anticonvulsant agents. Med Chem Res 22:5290–5296CrossRefGoogle Scholar
  11. Chen X, Meng Q, Qiu L, Zhan P, Liu H, DeClercq E, Pannecouque C, Liu X (2015) Design, synthesis, and anti-HIV evaluation of novel triazine derivatives targeting the entrance channel of the NNRTI binding pocket. Chem Biol Drug Des 86:122–128CrossRefPubMedGoogle Scholar
  12. Chen X, Zhan P, Liu X, Cheng Z, Meng C, Shao S, Pannecouque C, DeClercq E, Liu X (2012) Design, synthesis, anti-HIV evaluation and molecular modeling of piperidine-linked amino-triazine derivatives as potent non-nucleoside reverse transcriptase inhibitors. Bioorg Med Chem 20:3856–3864CrossRefPubMedGoogle Scholar
  13. Coates JA, Cammack N, Jenkinson HJ, Jowett AJ, Pearson BA, Penn CR, Rouse PL, Viner KC, Cameron JM (1992) The separated enantiomers of 2′-deoxy-3′-thiacytidine (BCH 189) both inhibit human immunodeficiency virus replication in vitro. Antimicrob Agents Chemother 36:733–739CrossRefPubMedPubMedCentralGoogle Scholar
  14. De Luca A, Dunn D, Zazzi M, Camacho R, Torti C, Fanti I, Kaiser R, Sonnerborg A, Codoñer FM, Van Laethem K, Vandamme AM, Bansi L, Ghisetti V, van de Vijver DA, Asboe D, Prosperi MC, Di Giambenedetto S, SEHERE Collaboration in Chain (2013) Declining prevalence of HIV-1 drug resistance in antiretroviral treatment-exposed individuals in Western Europe. J Infect Dis 207:1216–1220CrossRefPubMedGoogle Scholar
  15. de Silva TI, Cotton M, Rowland-Jones SL (2008) HIV-2: the forgotten AIDS virus. Trends Microbiol 16:588–595CrossRefPubMedGoogle Scholar
  16. Desai SD, Desai KR, Chikhalia KH, Pannecouque C, DeClercq E (2011) Int J Drug Des Discov 2:361–368Google Scholar
  17. El-Sabbagh OI, Baraka MM, Ibrahim SM, Pannecouque C, Andrei G, Snoeck R, Balzarini J, Rashad AA (2009) Synthesis and antiviral activity of new pyrazole and thiazole derivatives. Eur J Med Chem 44:3746–3753CrossRefPubMedGoogle Scholar
  18. Esté JA, Cihlar T (2010) Current status and challenges of antiretroviral research and therapy. Antiviral Res 85:25–33CrossRefPubMedGoogle Scholar
  19. Gomha SM, Badrey MG, Abdalla MM, Arafa RK (2014) Novel anti-HIV-1 NNRTIs based on a pyrazolo[4,3-d]isoxazole backbone scaffold: design, synthesis and insights into the molecular basis of action. Med Chem Commun 5:1685–1692CrossRefGoogle Scholar
  20. Haynes BF, Pantaleo G, Fauci AS (1996) Toward an understanding of the correlates of protective immunity to HIV infection. Science 271:324–328CrossRefPubMedGoogle Scholar
  21. Jaffar S, Grant AD, Whitworth J, Smith PG, Whittle H (2004) The natural history of HIV-1 and HIV-2 infections in adults in Africa: a literature review. Bull World Health Organ 82:462–469PubMedPubMedCentralGoogle Scholar
  22. Khan MH, Akhtar T, Yasin KA, Al-Masoudi NA, Jones PG, Hameed S (2010) Synthesis, crystal structure and biological evaluation of 6-adamantyl-3-aryl[1,2,4]triazolo[3,4-b][1,3,4] thiadiazoles. Z Naturforsch 65b:178–184Google Scholar
  23. Khan MH, Akhtar T, Al-Masoudi NA, Stoeckli-Evans H, Hameed S (2012) Synthesis, crystal structure and anti-HIV activity of 2-adamantyl /adamantylmethyl-5-aryl-1,3,4-oxadiazoles. Med Chem 8:1190–1197PubMedGoogle Scholar
  24. Khan MH, Hameed S, Farman M, Al- Masoudi NA, Stoeckli-Evans H (2015) Synthesis, anti HIV and molecular modeling study of 3-aryl-6-adamantyl-methyl-[1,2,4-]triazolo[3,4-b]thiazdiazole derivatives. Z Naturforsch 70b:609–616Google Scholar
  25. Khan MH, Hameed S, Akhtar T, Al-Masoudi NA, Al-Masoudi WA, Jones PG, Pannecouque C (2016) Synthesis, crystal structure, anti-HIV, and antiproliferative activity of new oxadiazole and thiazole analogs. Med Chem Res 25:2399–2409CrossRefGoogle Scholar
  26. Krečmerová M, Holý A, Pískala A, Masojídková M, Andrei G, Naesens L, Neyts L, Balzarini J, DeClercq E, Snoeck R (2007) Ester prodrugs of cyclic 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity. J Med Chem 50:1069–1077CrossRefPubMedGoogle Scholar
  27. Mitsuya H, Weinhold KJ, Furman PA, St. Clair MH, Lehrmann SN, Gallo R (1985) 3′-Azido-3′-deoxythymidine (BW A509U), an antiviral agent that inihibits the ineffectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associates virus in vitro. Proc Natl Acad Sci USA 82:7096–7100CrossRefPubMedPubMedCentralGoogle Scholar
  28. Miyoshi I, Taguchi H, Kobonishi I, Yoshimoto S, Ohtsuki Y, Shiraishi Y, Akagi T (1982) Type C virus-producing cell lines derived from adult T cell leukemia. Gann Monogr Cancer Res 28:219–228Google Scholar
  29. Nielsen SF, Christensen SB, Cruciani G, Kharazmi A, Liljefors T (1998) Antileishmanial chalcones: statistical design, synthesis, and three-dimensional quantitative structure–activity relationship analysis. J Med Chem 41:4819–4832CrossRefPubMedGoogle Scholar
  30. Panasci L, Jean-Claude BJ, Vasilescu D, Mustafa A, Damian S, Damian Z, Georges E, Liu Z, Liu Z, Batist G, Leyland-Jones B (1996) Sensitization to doxorubicin resistance in breast cancer cell lines by tamoxifen and megestrol acetate. Biochem Pharmacol 52:1097–1102Google Scholar
  31. Pandeya SN, Sriram D, Nath G, DeClercq E (1999) Synthesis, antibacterial, antifungal and anti-HIV activities of Schiff and Mannich bases derived from isatin derivatives and N-[4-(4′-chlorophenyl)thiazol-2-yl]thiosemicarbazide. Eur J Pharm Sci 9:25–31CrossRefPubMedGoogle Scholar
  32. Pannecouque C, Daelemans D, DeClercq E (2008) Tetrazolium-based colorimetric assay for the detection of HIV replication inhibitors:revisited, 20 years later. Nat Protoc 3:427–434CrossRefPubMedGoogle Scholar
  33. Pauwles R, Balzarini J, Baba M, Snoeck R, Schols D, Herdewijn P, Desmyter J, De Clercq E (1988) Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J Virol Methods 20:309–321CrossRefGoogle Scholar
  34. Popovic M, Sarngadharan MG, Read E, Gallo RC (1984) Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224:497–500CrossRefPubMedGoogle Scholar
  35. Rizvi SUF, Siddiqui HL, Johns M, Detorio M, Schinazi RF (2012) Anti-HIV-1 and cytotoxicity studies of piperidyl-thienyl chalcones and their 2-pyrazoline derivatives. Med Chem Res 21:3741–3749CrossRefGoogle Scholar
  36. Sarda S, Jadhav W, Bhusare S, Wasmatkar S, Dake S, Pawar R (2009) Solvent free NaOH Al2O3 supported synthesis of 1,3-diaryl-2-propene-1-ones. Int J Chem Tech Res 2:265–269Google Scholar
  37. Sheldrick GM (2015) Crystal structure refinement with SHELXL. Acta Cryst C71:3–8Google Scholar
  38. Siddiqui N, Arya SK, Ahsan W, Azad B (2011) Diverse biological activities of thiazoles: retrospect. Int J Drug Dev Res 3:55–67Google Scholar
  39. Tanemura K, Suzuki T, Nishida Y, Horaguchi T (2005) Aldol condensation in water using polyethylene glycol 400. Chem Lett 34:576–577CrossRefGoogle Scholar
  40. Tantawy AS, Nasr MNA, El-Sayed MA, El-Sayed MAA (2012) Synthesis and antiviral activity of new 3-methyl-1,5-diphenyl-1H-pyrazole derivatives. Med Chem Res 21:4139–4149CrossRefGoogle Scholar
  41. Tiberi M, Tintori C, Ceresola ER, Fazi R, Zamperini C, Calandro P, Franchi L, Selvaraj M, Botta L, Sampaolo M, Saita D, Ferrarese R, Clementi M, Canducci F, Botta M (2014) 2-Aminothiazolones as anti-HIV agents that act as gp120-CD4 Inhibitors. Antimicrob Agents Chemother 58:3043–3052CrossRefPubMedPubMedCentralGoogle Scholar
  42. Uyeki EM, Nishio A, Wittek PJ, Cheng CC (1981) Antiproliferative activity of doxorubicin and aminoanthraquinone derivatives on chinese hamster ovary cell. J Pharm Sci 70:1011–1014CrossRefPubMedGoogle Scholar
  43. Vicini P, Geronikaki A, Incerti M, Busonera B, Poni G, Cabras CA, La Colla P (2003) Synthesis and biological evaluation of benzo[d]isothiazole, benzothiazole and thiazole Schiff bases. Bioorg Med Chem 11:4785–4789CrossRefPubMedGoogle Scholar
  44. Willker W, Leibfritz D, Kerssebaum R, Bermel W (1993) Gradient selection in inverse heteronuclear correlation spectroscopy. Magn Reson Chem 31:287–292CrossRefGoogle Scholar
  45. Wu J, Shi Q, Chen Z, He M, Jin L, Hu D (2012) Synthesis and bioactivity of pyrazole acyl thiourea derivatives. Molecules 17:5139–5150CrossRefPubMedGoogle Scholar
  46. Xu Z, Ba M, Zhou H, Cao Y, Tang C, Yang Y, He R, Liang Y, Zhang X, Li Z (2014) 2,4,5-Trisubstitutedthiazole derivatives: a novel and potent class of non-nucleoside inhibitors of wild type and mutant HIV-1 reverse transcriptase. Eur J Med Chem 85:27–42CrossRefPubMedGoogle Scholar
  47. Zahid M, Yasin KA, Akhtar T, Rama NH, Hameed S, Al-Masoudi NA, Loddo R, La Colla P (2009) New 2-(4-aryl)-5-(2-adamantylthiazol-4-yl)-1,3,4-oxadiazoles as potential antiproliferative and antiviral agents. Arkivoc xi:85–93Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Murtaza Madni
    • 1
  • Shahid Hameed
    • 1
  • Muhammad N. Ahmed
    • 2
  • Muhammad N. Tahir
    • 3
  • Najim A. Al-Masoudi
    • 4
    • 6
  • Christophe Pannecouque
    • 5
  1. 1.Department of ChemistryQuaid-i-Azam UniversityIslamabadPakistan
  2. 2.Department of ChemistryThe University of Azad Jammu and KashmirMuzaffarabadPakistan
  3. 3.Department of PhysicsUniversity of SargodhaSargodhaPakistan
  4. 4.Department of Chemistry, College of ScienceUniversity of BasrahBasrahIraq
  5. 5.Rega Institute for Medical ResearchKatholieke Universiteit LeuvenLeuvenBelgium
  6. 6.KonstanzGermany

Personalised recommendations