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 [J].
Abdel-Aziz, Alaa A. -M. ;
El-Azab, Adel S. ;
Attia, Sabry M. ;
Al-Obaid, Abdulrahman M. ;
Al-Omar, Mohamed A. ;
El-Subbagh, Hussein I. .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (09) :4324-4329
[2]   Identification of KasA as the cellular target of an anti-tubercular scaffold [J].
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. .
NATURE COMMUNICATIONS, 2016, 7
[3]   In vitro activity and mechanism of action against the protozoan parasite Trypanosoma cruzi of 5-nitrofuryl containing thiosemicarbazones [J].
Aguirre, G ;
Boiani, L ;
Cerecetto, H ;
Fernández, M ;
González, M ;
Denicola, A ;
Otero, L ;
Gambino, D ;
Rigol, C ;
Olea-Azar, C ;
Faundez, M .
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 [J].
Akgun, Hulya ;
Karamelekoglu, Irem ;
Berk, Barkin ;
Kurnaz, Isil ;
Saribiyik, Gizem ;
Oktem, Sinem ;
Kocagoz, Tanil .
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 [J].
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. .
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 [J].
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 .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2015, 59 (03) :1398-1404
[8]   Optimization of Antitrypanosomatid Agents: Identification of Nonmutagenic Drug Candidates with in Vivo Activity [J].
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 .
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