Privileged Structures in the Design of Potential Drug Candidates for Neglected Diseases

被引:37
作者
Lima Leite, Ana Cristina [1 ]
Pontes Espindola, Jose Wanderlan [1 ]
de Oliveira Cardoso, Marcos Verissimo [2 ]
de Oliveira Filho, Gevanio Bezerra [1 ,3 ]
机构
[1] Univ Fed Pernambuco, Ctr Ciencias Saude, Dept Ciencias Farmaceut, BR-50740520 Recife, PE, Brazil
[2] Univ Pernambuco, Colegiado Nutr, Campus Petrolina, BR-56328903 Petrolina, PE, Brazil
[3] Fac Integracao Sertao, Rua Joao Luiz de Melo 2110, Serra Talhada, PE, Brazil
关键词
Privileged structures; phthalimide; isatine; indole; thiosemicarbazone; thiazole; thiazolidinone antiprotozoal chemotherapy; leishmania; plasmodium; trypanosoma; antiparasitic drugs; MYCOBACTERIUM-TUBERCULOSIS ACTIVITY; IN-VITRO ACTIVITY; TRYPANOSOMA-CRUZI; BIOLOGICAL EVALUATION; PHARMACOLOGICAL EVALUATION; ANTIMICROBIAL ACTIVITIES; PHTHALIMIDE DERIVATIVES; PLASMODIUM-FALCIPARUM; ANTIMALARIAL ACTIVITY; SELECTIVE INHIBITORS;
D O I
10.2174/0929867324666171023163752
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Privileged motifs are recurring in a wide range of biologically active compounds that reach different pharmaceutical targets and pathways and could represent a suitable start point to access potential candidates in the neglected diseases field. The current therapies to treat these diseases are based in drugs that lack of the desired effectiveness, affordable methods of synthesis and allow a way to emergence of resistant strains. Due the lack of financial return, only few pharmaceutical companies have been investing in research for new therapeutics for neglected diseases (ND). Methods: Based on the literature search from 2002 to 2016, we discuss how six privileged motifs, focusing phthalimide, isatin, indole, thiosemicarbazone, thiazole, and thiazolidinone are particularly recurrent in compounds active against some of neglected diseases. Results: It was observed that attention was paid particularly for Chagas disease, malaria, tuberculosis, schistosomiasis, leishmaniasis, dengue, African sleeping sickness (Human African Trypanosomiasis - HAT) and toxoplasmosis. It was possible to verify that, among the ND, antitrypanosomal and antiplasmodial activities were between the most searched. Besides, thiosemicarbazone moiety seems to be the most versatile and frequently explored scaffold. As well, phthalimide, isatin, thiazole, and thiazolidone nucleus have been also explored in the ND field. Conclusion: Some described compounds, appear to be promising drug candidates, while others could represent a valuable inspiration in the research for new lead compounds.
引用
收藏
页码:4323 / 4354
页数:32
相关论文
共 178 条
  • [1] Synthesis and biological evaluation of some novel cyclic-imides as hypoglycaemic, anti-hyperlipidemic agents
    Abdel-Aziz, Alaa A. -M.
    El-Azab, Adel S.
    Attia, Sabry M.
    Al-Obaid, Abdulrahman M.
    Al-Omar, Mohamed A.
    El-Subbagh, Hussein I.
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (09) : 4324 - 4329
  • [2] Identification of KasA as the cellular target of an anti-tubercular scaffold
    Abrahams, Katherine A.
    Chung, Chun-wa
    Ghidelli-Disse, Sonja
    Rullas, Joaquin
    Jose Rebollo-Lopez, Maria
    Gurcha, Sudagar S.
    Cox, Jonathan A. G.
    Mendoza, Alfonso
    Jimenez-Navarro, Elena
    Santos Martinez-Martinez, Maria
    Neu, Margarete
    Shillings, Anthony
    Homes, Paul
    Argyrou, Argyrides
    Casanueva, Ruth
    Loman, Nicholas J.
    Moynihan, Patrick J.
    Lelievre, Joel
    Selenski, Carolyn
    Axtman, Matthew
    Kremer, Laurent
    Bantscheff, Marcus
    Angulo-Barturen, Inigo
    Cacho Izquierdo, Monica
    Cammack, Nicholas C.
    Drewes, Gerard
    Ballell, Lluis
    Barros, David
    Besra, Gurdyal S.
    Bates, Robert H.
    [J]. NATURE COMMUNICATIONS, 2016, 7
  • [3] In vitro activity and mechanism of action against the protozoan parasite Trypanosoma cruzi of 5-nitrofuryl containing thiosemicarbazones
    Aguirre, G
    Boiani, L
    Cerecetto, H
    Fernández, M
    González, M
    Denicola, A
    Otero, L
    Gambino, D
    Rigol, C
    Olea-Azar, C
    Faundez, M
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (18) : 4885 - 4893
  • [4] Ahsan M.J., 2016, J BASIC APPL SCI, V5, P119
  • [5] Synthesis and antimycobacterial activity of some phthalimide derivatives
    Akgun, Hulya
    Karamelekoglu, Irem
    Berk, Barkin
    Kurnaz, Isil
    Saribiyik, Gizem
    Oktem, Sinem
    Kocagoz, Tanil
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (13) : 4149 - 4154
  • [6] Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: Anti-inflammatory and analgesic activities
    Alanazi, Amer M.
    El-Azab, Adel S.
    Al-Suwaidan, Ibrahim A.
    ElTahir, Kamal Eldin H.
    Asiri, Yousif A.
    Abdel-Aziz, Naglaa I.
    Abdel-Aziz, Alaa A. -M.
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 92 : 115 - 123
  • [7] Identification of a New Amide-Containing Thiazole as a Drug Candidate for Treatment of Chagas' Disease
    Alvarez, Guzman
    Varela, Javier
    Cruces, Eugenia
    Fernandez, Marcelo
    Gabay, Martin
    Leal, Sandra M.
    Escobar, Patricia
    Sanabria, Luis
    Serna, Elva
    Torres, Susana
    Thiel, Susy J. Figueredo
    Yaluff, Gloria
    de Bilbao, Ninfa I. Vera
    Cerecetto, Hugo
    Gonzalez, Mercedes
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2015, 59 (03) : 1398 - 1404
  • [8] Optimization of Antitrypanosomatid Agents: Identification of Nonmutagenic Drug Candidates with in Vivo Activity
    Alvarez, Guzman
    Varela, Javier
    Marquez, Pablo
    Gabay, Martin
    Arias Rivas, Carmen Elena
    Cuchilla, Karina
    Echeverria, Gustavo A.
    Piro, Oscar E.
    Chorilli, Marlus
    Leal, Sandra M.
    Escobar, Patricia
    Serna, Elva
    Torres, Susana
    Yaluff, Gloria
    Vera de Bilbao, Ninfa I.
    Gonzalez, Mercedes
    Cerecetto, Hugo
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (10) : 3984 - 3999
  • [9] ALVES AJ, 1993, FARMACO, V48, P1167
  • [10] [Anonymous], 1869, BER DTSCH CHEM GES, DOI DOI 10.1002/CBER.186900201293