Synthesis, crystal structure, anti-HIV, and antiproliferative activity of new oxadiazole and thiazole analogs

被引：41

作者：

Khan, Mahmood-ul-Hassan ^{[1
]}

Hameed, Shahid ^{[1
]}

Akhtar, Tashfeen ^{[1
,2
]}

Al-Masoudi, Najim A. ^{[3
]}

Al-Masoudi, Wasfi A. ^{[4
]}

Jones, Peter G. ^{[5
]}

Pannecouque, Christophe ^{[6
]}

机构：

[1] Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan

[2] Mirpur Univ Sci & Technol MUST, Dept Chem, Mirpur, Azad Jammu & Ka, Pakistan

[3] Univ Basrah, Dept Chem, Coll Sci, Basrah, Iraq

[4] Univ Basrah, Dept Physiol Pharmacol & Chem, Coll Vet Med, Basrah, Iraq

[5] Tech Univ Carolo Wilhelmina Braunschweig, Inst Anorgan & Analyt Chem, Hagenring 30, D-38106 Braunschweig, Germany

[6] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Leuven, Belgium

来源：

MEDICINAL CHEMISTRY RESEARCH | 2016年 / 25卷 / 10期

关键词：

Anti-HIV activity; Antiproliferative activity; Adamantyl derivatives; Oxadiazole; Thiazoles; REVERSE-TRANSCRIPTASE INHIBITORS; NONNUCLEOSIDE INHIBITORS; COLORIMETRIC ASSAY; PETT COMPOUNDS; DERIVATIVES; 1,3,4-OXADIAZOLE-2-THIONE; DISCOVERY; THIOUREA; DRUGS;

D O I：

10.1007/s00044-016-1669-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 2-adamantyl-5-arylthiazolyl-1,3,4-oxadiazoles 7a-x together with thiazoles 13 and 14 were synthesized. Compounds 7a-l, 13, and 14 were tested in vitro with the aim of identifying novel lead compounds active against human immunodeficiency virus type-1 and human immunodeficiency virus type-2 activity in MT-4 cells. Title compounds were also tested against representatives of Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Salmonella spp.), various mycobacterial strains (Mycobacterium fortuitum and Mycobacterium smegmatis), yeast (Candida albicans), and mold (Aspergillus fumigatus). None of the compounds showed antiviral or antimicrobial activity, except compounds 13 and 14 exhibited anti-human immunodeficiency virus-1 activity with EC50 values of 1.79 and 2.39 mu M with Selectivity index = 18 and 4, respectively. On the other hand, compounds 7a and 7j showed a marked cytotoxicity against the human CD4(+) lymphocytes (MT-4). Therefore, 7a and 7j were evaluated for their antiproliferative activity against two solid tumor-derived cell lines, which exhibited IC50 values of 8.1 +/- 0.10 A mu M and 4.8 A +/- 0.08 A mu M against Hep-G2 cell lines, respectively.

引用

页码：2399 / 2409

页数：11

共 39 条

[11] Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents [J].

Dawood, Kamal M. ;

Eldebss, Taha M. A. ;

El-Zahabi, Heba S. A. ;

Yousef, Mahmoud H. ;

Metz, Peter .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 70 :740-749

[12] Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV [J].

De Clercq, Erik .

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2009, 33 (04) :307-320

[13]

de Souza M.V.N., 2011, Glob. View HIV Infect., P127

[14] THE REACTION OF KETONES WITH HALOGENS AND THIOUREA [J].

DODSON, RM ;

KING, LC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1945, 67 (12) :2242-2243

[15] NOVEL NONNUCLEOSIDE INHIBITORS OF HIV-1 REVERSE-TRANSCRIPTASE .1. TRICYCLIC PYRIDOBENZODIAZEPINONES AND DIPYRIDODIAZEPINONES [J].

HARGRAVE, KD ;

PROUDFOOT, JR ;

GROZINGER, KG ;

CULLEN, E ;

KAPADIA, SR ;

PATEL, UR ;

FUCHS, VU ;

MAULDIN, SC ;

VITOUS, J ;

BEHNKE, ML ;

KLUNDER, JM ;

PAL, K ;

SKILES, JW ;

MCNEIL, DW ;

ROSE, JM ;

CHOW, GC ;

SKOOG, MT ;

WU, JC ;

SCHMIDT, G ;

ENGEL, WW ;

EBERLEIN, WG ;

SABOE, TD ;

CAMPBELL, SJ ;

ROSENTHAL, AS ;

ADAMS, J .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (07) :2231-2241

[16] The inhibitory activity of diazinyl-substituted thiourea derivatives on human immunodeficiency virus type 1 reverse transcriptase [J].

Heinisch, G ;

Matuszczak, B ;

Pachler, S ;

Rakowitz, D .

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1997, 8 (05) :443-446

[17] Action of Anti-HIV drugs and resistance: Reverse transcriptase inhibitors and protease inhibitors [J].

Imamichi, T .

CURRENT PHARMACEUTICAL DESIGN, 2004, 10 (32) :4039-4053

[18]

Jonckheere H, 2000, MED RES REV, V20, P129, DOI 10.1002/(SICI)1098-1128(200003)20:2<129::AID-MED2>3.0.CO

[19]

2-A

[20]

Kabbani AT, 2005, U CHEM TECHN METAL, V40, P339

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