ORIGINAL ARTICLE
Received:20/18/02/28 Accepted:2018/05/05
Synthesis and in Vitro Evaluation of Antifungal and Antibacterial Activity of 2,3-Dihydroquinazolinone Derivatives
Fatemeh Tamaddon (Ph.D.)1, Behnoosh Moradi (M.Sc.)2, Alireza Nasiri (Ph.D.)3, Fatemeh Rahbar (B.S.)4
1.Corresponding Author:Associate Professor, Department of Chemistry, Faculty of Science, Yazd University, Yazd, Iran. Email: [email protected] Tel: 09121300186
2.MS.c, Department of Chemistry, Faculty of Science, Yazd University, Yazd, Iran.
3.Ph.D. Student, Faculty of Chemistry, Islamic Azad University, Yazd Branch, Yazd, Iran and Environmental Health Engineering Research Center, Kerman University of Medical Sciences, Kerman, Iran.
4.B.S. Student, Islamic Azad University Tehran Medical Branch, Tehran, Iran.
Abstract
Introduction: By development of bacterial drug-resistance to traditional antibacterial drugs and fungal infections, the need to design, synthesis, and use of new and effective antibacterial and antifungal drugs is increased. Quinazolinone derivatives are heterocyclic compounds with nitrogen atoms that have pharmacological properties such as anti-bacterial, anti-tumor, anti-inflammatory and antifungal properties.
The aim of this study was to synthesize of new derivatives of dihydroquinazolinone and study of their anti- bacterial and antifungal properties.
Methods:This research is an experimental work in which four dihydroquinazolinone derivatives were synthesized, by a new environmental-safe method and identified by various spectroscopic methods.
Antibacterial activities of these derivatives were investigated against Escherichia coli gram-negative, and bacillus subtilis gram-positive in comparesion with amikacin. Antifungal activities of these derivatives were investigated against Aspergillusniger fungus and compared with ketoconazole.Both of antifungal and antibacterial activities of these synthetic compounds derivatives was checked by disk diffusion method with measuring the zone inhibition.
Results: All synthetic dihydroquinazolinones that were synthesized in high yields and purity, showed good antibacterial and antifungal properties.The compound 1d 2-phenyl-2,3-dihydroquinazolin-4(1H)-one derivative of these compounds showed more antimicrobial activitiesand antifungal comparable with the Amikacin and Ketoconazole standard antibacterial and antifungal drugs.
Conclusion: Synthetic dihydroquinazolinone derivatives in this work have good antifungal and antibacterial activities. The higher antifungal and antibacterial activity of 2-phenyl-2,3-dihydroquinazolin-4(1H)-one derivative can be related to more hydrophobicity of the phenyl group as a substitution in position 2.
Keywords: Anti-bacterial, Anti-fungal, Dihydroquinazolinone
Conflict of interest: The authors declared that there is no Conflict of interests.
This Paper Should be Cited as:
Author:Fatemeh Tamaddon, Behnoosh Moradi, Alireza Nasiri, Fatemeh Rahbar.
Synthesis and in Vitro Evaluation of Antifungal and Antibacterial, ……
Tolooebehdasht Journal.2018; 17(3):77-85 .[Persian]
ود ﻲﺸﻫوﮋﭘ ﻲﻤﻠﻋ ﻪﻣﺎﻨﻫﺎﻣ دﺰﻳ ﺖﺷاﺪﻬﺑ عﻮﻠﻃ
لﺎﺳ و دادﺮﻣ، مﻮﺳ هرﺎﻤﺷ،ﻢﻫﺪﻔﻫ رﻮﻳﺮﻬﺷ
1397
ﻮﻧ نﺎﮔﺪﻨﺴﻳ نﺪﻤﺗ ﻪﻤﻃﺎﻓ : داﺮﻣ شﻮﻨﻬﺑ ،1
2ي ﻠﻋ ، ﺎﺿﺮﻴ ﺼﻧ
3يﺮﻴ ﺮﺒﻫر ﻪﻤﻃﺎﻓ ،
4
1 :لﻮﺌﺴﻣ هﺪﻨﺴﻳﻮﻧ.
ﺸﻧاد هوﺮﮔ رﺎﻴ ﺷ ﻲﻤﻴ ﻟآ ﻲ
، ﺷ هﺪﻜﺸﻧاد
،ﻲﻤﻴ هﺎﮕﺸﻧاد ،مﻮﻠﻋ ﻊﻤﺘﺠﻣ دﺰﻳ
.ناﺮﻳا،دﺰﻳ،
ﻦﻔﻠﺗ سﺎﻤﺗ : 09121300186 Email: [email protected]
2 . ﺷ ﺪﺷرا سﺎﻨﺷرﺎﻛ ﻲﻤﻴ
ﻟآ
،ﻲ ﺷ هﺪﻜﺸﻧاد
،ﻲﻤﻴ
،مﻮﻠﻋ ﻊﻤﺘﺠﻣ هﺎﮕﺸﻧاد
دﺰﻳ .ناﺮﻳا،دﺰﻳ،
3 . ﻮﺠﺸﻧاد ي ﺮﺘﻛد ي ﺷ ﻲﻤﻴ ﻟآ
،ﻲ ﺷ هﺪﻜﺸﻧاد
،ﻲﻤﻴ ﻣﻼﺳا دازآ هﺎﮕﺸﻧاد
،ﻲ ﺪﺣاو دﺰﻳ ﻘﺤﺗ ﺰﻛﺮﻣ ﺮﮕﺸﻫوﮋﭘ و تﺎﻘﻴ
ﺳﺪﻨﻬﻣ ﻲ ﺖﺷاﺪﻬﺑ
ﺤﻣ ﻂﻴ ﻜﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ﻲ
نﺎﻣﺮﻛ .ناﺮﻳا،نﺎﻣﺮﻛ،
4 . ﻮﺠﺸﻧاد ي ﺳﺎﻨﺷرﺎﻛ ﻲ ﺘﻧژ
،ﻚﻴ
،ﺖﺷاﺪﻬﺑ هﺪﻜﺸﻧاد ﻣﻼﺳا دازآ هﺎﮕﺸﻧاد
.ناﺮﻳا،ناﺮﻬﺗ،ناﺮﻬﺗ ﻲ
ﺖﺷاﺪﻬﺑ عﻮﻠﻃ
ﻲﻤﻠﻋ ﻪﻣﺎﻨﻫﺎﻣ ود ﻲﺸﻫوﮋﭘ
دﺰﻳ ﺖﺷاﺪﻬﺑ هﺪﻜﺸﻧاد ﻢﻫﺪﻔﻫ لﺎﺳ مﻮﺳ:هرﺎﻤﺷ رﻮﻳﺮﻬﺷ و دادﺮﻣ 1397
:ﻞﺴﻠﺴﻣ هرﺎﻤﺷ 69
:لﻮﺻو ﺦﻳرﺎﺗ 09
/ 12 / 1396
:شﺮﻳﺬﭘ ﺦﻳرﺎﺗ 15
/ 02 / 1397 هﺪﻴﻜﭼ
:ﻪﻣﺪﻘﻣ ﺮﺘﻛﺎﺑ ﺖﻣوﺎﻘﻣ شﺮﺘﺴﮔ ﺎﺑ ي
ﺎﻫ ﺎﻫوراد ﻪﺑ ي ﺮﺘﻛﺎﺑ ﺪﺿ ﻲﻳﺎﻳ ﺘﻨﺳ ﻲ اﺰﻓا و ﺶﻳ ﻋ ﺖﻧﻮﻔ يﺎﻫ ﭼرﺎﻗ
،ﻲ ﻧ زﺎﻴ
ﺣاﺮﻃ ﻪﺑ
،ﻲ ﺎﻫوراد زا هدﺎﻔﺘﺳا و ﺰﺘﻨﺳ ي
ﺪﺟ ﺪﻳ ﺪﺿ ﺮﺛﻮﻣ و ﺮﺘﻛﺎﺑ
ي ﺪﺿ و چرﺎﻗ ﺮﺘﺸﻴﺑ ﻣ ﻲ دﻮﺷ تﺎﻘﺘﺸﻣ .
ﻛ ﻴ ﻟوزﺎﻨ نﻮﻨﻴ ﻛﺮﺗ تﺎﺒﻴ ﺳوﺮﺘﻫ ﻢﺗا ود ياراد ﻞﻜﻴ ﻧ
صاﻮﺧ ﺎﺑ نژوﺮﺘﻴ ژﻮﻟﻮﻛﺎﻣرﺎﻓ
ﻲﻜﻳ ﺪﺿ
،ﻲﻳﺎﻳﺮﺘﻛﺎﺑ
ﺪﺿ و بﺎﻬﺘﻟا ﺪﺿ ،رﻮﻣﻮﺗﺪﺿ ﭼرﺎﻗ
ﻲ ،ﻖﻴﻘﺤﺗ ﻦﻳا فﺪﻫ .ﺪﻨﺘﺴﻫ ﺰﺘﻨﺳ
تﺎﺒﻴﻛﺮﺗ ﺪﺟ ﺪﻳ د ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ
و ﻲﺳرﺮﺑ ﺮﺘﻛﺎﺑﺪﺿ صاﻮﺧ ﻲﻳﺎﻳ
ﺪﺿ و ﻲﭼرﺎﻗ نآ .ﺖﺳا ﺎﻫ
ﻲﺳرﺮﺑ شور نآ رد و ﺖﺳا ﻲﺑﺮﺠﺗ ﻖﻴﻘﺤﺗ ﻦﻳا :
رﺎﻬﭼ ﻛﺮﺗ زا ﻖﺘﺸﻣ تﺎﺒﻴ
د ي ﻫ ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴ ﻖﻳﺮﻃ زا
ﻚﻳ ﺪﺟ شور و ﺪﻳ
ﺤﻣ ﺎﺑ رﺎﮔزﺎﺳ ًﻼﻣﺎﻛ ﻂﻴ
ز ﺖﺴﻳ رﺎﺘﺧﺎﺳ و ﺰﺘﻨﺳ بآ رد ﺎﻬﻧآ
ﻂﺳﻮﺗ شور يﺎﻫ
ﭘﻮﻜﺳوﺮﺘﻜﭙﺳا ﻲ
ﺎﺳﺎﻨﺷ ﻒﻠﺘﺨﻣ ﻲﻳ
ﺄﺗ و ﺪﻴﻳ ﺪﺷ . ﻟﺎﻌﻓ ﺖﻴ ﺪﺿ ﺮﺘﻛﺎﺑ ﻲﻳﺎﻳ ا ﻦﻳ ﻛﺮﺗ تﺎﺒﻴ ﻪﻴﻠﻋ ﺮﺘﻛﺎﺑ ي يﺎﻫ مﺮﮔ
ﻔﻨﻣ ﻲ ﺷﺮﺷا و ﻲﻠﻛﺎﻴ ﺳﺎﺑ ﺖﺒﺜﻣ مﺮﮔ سﻮﻠﻴ
ﻠﺘﺑﻮﺳ ﺲﻴ ﺎﺑ ﻪﺴﻳﺎﻘﻣ رد يوراد
ﻣآ و ﻦﻴﺳﺎﻜﻴ ﻟﺎﻌﻓ
ﺖﻴ ﺪﺿ نآ ﻲﭼرﺎﻗ ﺎﻫ
ﻪﻴﻠﻋ ژﺮﭙﺳآ چرﺎﻗ سﻮﻠﻳ
ﻧ يوراد ﺎﺑ ﻪﺴﻳﺎﻘﻣ رد ﺮﺠﻴ ﻂﺳﻮﺗ لوزﺎﻧﻮﻛﻮﺘﻛ
د نﻮﻣزآ ﻚﺴﻳ د يﺮﻴﮔ هزاﺪﻧا ﺎﺑ نژﻮﻴﻔﻳ
ﺪﺷر مﺪﻋ ﻪﻟﺎﻫ .ﺪﺷ ﻲﺳرﺮﺑ
:ﺎﻫ ﻪﺘﻓﺎﻳ ﻲﻣﺎﻤﺗ ﻪﭼﺮﮔا
ﻘﺘﺸﻣ تﺎ د ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ ﺪﺿ صاﻮﺧ ،ﻻﺎﺑ صﻮﻠﺧ و هدزﺎﺑ ﺎﺑ هﺪﺷ ﺰﺘﻨﺳ
ﺮﺘﻛﺎﺑ ﻲﭼرﺎﻗ ﺪﺿو ﻲﻳﺎﻳ ﻲﺒﺳﺎﻨﻣ
ﺪﻧداد نﺎﺸﻧ دﻮﺧ زا
، ﻖﺘﺸﻣ 2 - ﻞﻴﻨﻓ - 2 و 3 - يد ﻦﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ -
4 - H) ( - نوا
ﻟﺎﻌﻓ ﺖﻴ ﺑ ﺮﺘﺸﻴ ﺎﻘﻣ ﻞﺑﺎﻗ و ﻪﺴﻳ
يا ﺎﻫوراد ﺪﺣ رد ي
ﺮﺘﻛﺎﺑ ﺪﺿ دراﺪﻧﺎﺘﺳا ي
ﻣآ ﻦﻴﺳﺎﻜﻴ زا لوزﺎﻧﻮﻛﻮﺘﻛ چرﺎﻗ ﺪﺿ و
.داد نﺎﺸﻧ دﻮﺧ :يﺮﻴﮔ ﻪﺠﻴﺘﻧ ﻛﺮﺗ
تﺎﺒﻴ د ي ﻫ ورﺪﻴ ﻛ ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴ ،ﻖﻴﻘﺤﺗ ﻦﻳا رد يﺰﺘﻨﺳ
ﻟﺎﻌﻓ ﺖﻴ ﭼرﺎﻗ ﺪﺿ ﻲ ﺮﺘﻛﺎﺑ ﺪﺿو ﻲﻳﺎﻳ
ﻲﺒﺳﺎﻨﻣ ﺪﻧراد . ﺮﺘﺸﻴﺑ ﺖﻴﻟﺎﻌﻓ ﺪﺿ
ﭼرﺎﻗ ﻲ ﺪﺿ و ﺮﺘﻛﺎﺑ ي ﻖﺘﺸﻣ 2 - ﻨﻓ ﻞﻴ - 2 و 3 - د ي ﻫ ﻦﻴﻟوزﺎﻨﻴﻛورﺪﻴ -
4 - H) ( - نوا
ﻣ ار ﻲ ناﻮﺗ ﺑ ﻪ ﺑآ يﺰﻳﺮﮕ ﺑ ﺮﺘﺸﻴ ﻨﻓ ﺔﻘﻠﺣ ﻞﻴ ﻌﻗﻮﻣ رد فﻼﺨﺘﺳا نوﺪﺑ ﺖﻴ
2 - ﻛﺮﺗ ﺐﻴ ﺎﻘﻣ رد ﻪﺴﻳ ﺎﺳ ﺎﺑ ﺮﻳ تﺎﻘﺘﺸﻣ
هوﺮﮔ ياراد ﺖﺳوﺪﺑآ يﺎﻫ
ﺮﺗ ﺖﻴﻌﻗﻮﻣ ﻦﻳا رد .ﺖﺴﻧاد طﻮﺑﺮﻣ
:يﺪﻴﻠﻛ يﺎﻫ هژاو ﺮﺘﻛﺎﺑﺪﺿ
،ﻲﻳﺎﻳ ،چرﺎﻗ ﺪﺿ تﺎﻘﺘﺸﻣ
د ي نﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ
ود ﻲﺸﻫوﮋﭘ ﻲﻤﻠﻋ ﻪﻣﺎﻨﻫﺎﻣ دﺰﻳ ﺖﺷاﺪﻬﺑ عﻮﻠﻃ
لﺎﺳ رﻮﻳﺮﻬﺷ و دادﺮﻣ، مﻮﺳ هرﺎﻤﺷ،ﻢﻫﺪﻔﻫ 1397
ﻪﻣﺪﻘﻣ وراد ﺖﻣوﺎﻘﻣ شﺮﺘﺴﮔ ﻪﺑ ور ﺪﻧور ﻲﻳ
ﺮﺘﻛﺎﺑ ي ﺎﻫ چرﺎﻗ و ﺎﻫ رد ﻪﻫد
ﻪﺘﺷﺬﮔ ﺮﺠﻨﻣ ﻪﺑ ﺶﻳاﺰﻓا آ ﻘﺤﺗ رﺎﻣ تﺎﻘﻴ ﻣز رد ﻪﻨﻴ ﺣاﺮﻃ ﻲ ﺎﻫوراد ي
ﺪﺟ ﺪﻳ هﺪﺷ .ﺖﺳا ا رد ﻦﻳ ﺎﺘﺳار
، ﺎﻫوراد ي ﺪﺟ ﺪﻳ و چرﺎﻗﺪﺿ
ﺮﺘﻛﺎﺑﺪﺿ ي ﻧﺎﻜﻣ ﺎﺑ ﻢﺴﻴ دﺮﻜﻠﻤﻋ ي اﺮﺑ توﺎﻔﺘﻣ ي
ا لﺮﺘﻨﻛ ﻦﻳ عﻮﻧ
ﺖﻧﻮﻔﻋ ﺎﻫ رد ﻚﻴﻨﻴﻠﻛ ﻓﺮﮔ راﺮﻗ هدﺎﻔﺘﺳا درﻮﻣ ﺎﻫ ﻪﺘ
ﺪﻧا ﺎﺷ ﻪﻛ ﺪﻳ
ﻛﺮﺗ ناﻮﺘﺑ تﺎﺒﻴ
ﺳوﺮﺘﻫ ﻞﻜﻴ ﻧ نژوﺮﺘﻴ راد ﻢﻬﻣ زا ار ﻦﻳﺮﺗ
نآ ﺎﻫ
) ﺖﺴﻧاد 5
- 1 ( . تﺎﻘﺘﺸﻣ ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛ
ﻛﺮﺗ ﻪﻠﻤﺟ زا تﺎﺒﻴ
ﺳوﺮﺘﻫ ﻞﻜﻴ وراد ﻲﻳ ﻧ ﻢﺗا ود ﺎﺑ نژوﺮﺘﻴ ﺪﻨﺘﺴﻫ ﻪﻛ رد ﺴﺑ نﺎﻣرد يرﺎﻴ
ﺑ زا يرﺎﻤﻴ يﺎﻫ ا دﺎﺠﻳ ﻣ ﻂﺳﻮﺗ هﺪﺷ ﻢﺴﻴﻧﺎﮔراوﺮﻜﻴ
ﺎﻫ رﺎﻛ ﻪﺑ
ﻣ ﻲ ﺪﻧور ) 6
،هوﻼﻋ ﻪﺑ .(
ﻓ ﺖﻴﻟﺎﻌ يﺎﻫ وراد ﻲﻳ د يﺮﮕﻳ صاﻮﺧ ﻞﻣﺎﺷ
ﺮﺘﻛﺎﺑ ﺪﺿ
،ﻲﻳﺎﻳ رﻮﻣﻮﺗ ﺪﺿ
،ي ﭼرﺎﻗ ﺪﺿ
،ﻲ ﻓ ﺪﺿ
،يﺮﺒﻴ و
ﮔﺪﻨﻨﻛدﺎﺸﮔ ﻲ
قوﺮﻋ ﺖﺳا هﺪﺷ شراﺰﮔ تﺎﺒﻴﻛﺮﺗ ﻦﻳا ياﺮﺑ
) 9 - 7 ﻞﻜﺷ ﻪﻛ ( 1
ﻲﻣ نﺎﺸﻧ ار ﺎﻬﻧآ زا ﻲﻫوﺮﮔ )ﺪﻫد
7 .(
ﻪﺑ ﻞﻴﻟد ﺴﻧﺎﺘﭘ ﻞﻴ وراد ﻲﻳ ز دﺎﻳ ا ﻦﻳ ﻛﺮﺗ
،تﺎﺒﻴ شور يﺎﻫ ﻋﻮﻨﺘﻣ ﻲ ﻢﻫ
اﺮﺑ ي ﺰﺘﻨﺳ نآ ﻲﻤﻴﺷ ﻊﺑﺎﻨﻣ رد ﺎﻫ را
ا هﺪﺷ ﻪﺋ Sharma .ﺖﺳا
و
لﺎﺳ رد Kaur 1989 زا ﺶﻨﻛاو ﺘﻧآ ﻞﻴﻧاﺮ آ ﻣ ﺪﻴ ﺎﺑ ﺋﺪﻟآ ﺪﻴ ﺎﻫ و نﻮﺘﻛ
ﺎﻫ ﻒﻠﺘﺨﻣ ي ﻟﺎﺗﺎﻛ رﻮﻀﺣ رد
يﺪﻴﺳا ﺖﺴﻴ ﻮﻟﻮﺗارﺎﭘ
ﻦﺋ
ﻟﻮﺳ ـ ﻧﻮﻔ ﻚﻴ ﺳا ـ ﺪﻴ ﺷ رد ـ اﺮ ﻳـ ﻂ ر ﻓـ ﻛﻼ ـ ﺲ ﻴﻛﺮﺗ ـ تﺎﺒ
د ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ ) ﺪﻧدﺮﻛ ﺰﺘﻨﺳ ار
10 .(
ﻤﺘﺳر ﻲ و هداز
نارﺎﻜﻤﻫ لﺎﺳ رد
2008 ﺶﻨﻛاو زا ا
ﻚﻴﺋﻮﺗاﺰﻳ ﺪﻳرﺪﻴﻧا
ﺎﺑ
ﺋﺪﻟآ يﺎﻫﺪﻴ ﻚﻴﺗﺎﻣورآ اﺮﺷ رد
ﻂﻳ نوﺪﺑ لﻼﺣ رﻮﻀﺣ رد
ﻟﺎﺗﺎﻛ روﺰﻴ تﺎﺒﻴﻛﺮﺗ ﺪﻳ د
ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ ﺪﻧدﺮﻛ ﺰﺘﻨﺳ ار
) 11 ﻢﻫ .(
ﺖﺴﻴﻟﺎﺗﺎﻛ زا ﻦﻴﻨﭼ يﺎﻫ
ﺋﻮﻟ ﺲﻴ ﺳا يﺪﻴ ﻟﺎﮔ ﻢﻴ -يﺮﺗ
) تﻻﺎﺘﻓ 12 ( ور و ي ) تاﻮﻧﺎﺘﻛاورﻮﺋﻮﻠﻓﺮﭘ 13
( اﺮﺑ ي ﻊﻳﺮﺴﺗ ﺰﺘﻨﺳ
نﻮﻨﻴﻟوزﺎﻨﻴﻛ .ﺖﺳا هﺪﺷ هدﺎﻔﺘﺳا ﺎﻫ
Bunce Nammalwar و
رد
لﺎﺳ 2011 زا هدﺎﻔﺘﺳا ﺎﺑ 2
- ﻧ ﺪﻴﻣاﺰﻨﺑوﺮﺘﻴ و ﺎﻫ
تﺎﺒﻴﻛﺮﺗ ﺑﺮﻛ ﻞﻴﻨ راد
رﻮﻀﺣ رد ﻒﻠﺘﺨﻣ ﻟﺎﺗﺎﻛ
ﺖﺴﻴ ﻦﻫآ ردﻮﭘ نﻮﻨﻴﻟوزﺎﻨﻴﻛ تﺎﻘﺘﺸﻣ ،
ار ﺰﺘﻨﺳ ) ﺪﻧدﺮﻛ 14 Ramesh .(
نارﺎﻜﻤﻫ و لﺎﺳ رد
2012
تﺎﻘﺘﺸﻣ د ي ﻫ ﻞﻴﻧاﺮﺘﻧآ ﺶﻨﻛاو زا ار نﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴ و ﺪﻴﻣآ
بآ لﻼﺣ رد ﻦﻳﺮﺘﺴﻛدﻮﻠﻜﻴﺳﺎﺘﺑ رﻮﻀﺣ رد ﻒﻠﺘﺨﻣ يﺎﻫﺪﻴﺋﺪﻟآ ) ﺪﻧدﺮﻛ ﺰﺘﻨﺳ 15
Langer (.
نارﺎﻜﻤﻫ و لﺎﺳ رد ﺰﻴﻧ
2014 زا
ﺶﻨﻛاو 2 - ﻣآ ﻞﻳﺮﺘﻴﻧوﺰﻨﺑﻮﻨﻴ ﺋﺪﻟآ و
ﺪﻴ ﺎﻫ ي ﻚﻴﺗﺎﻣورآ بآ رد
تﺎﻘﺘﺸﻣ د ي ﻫ نﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴ ار
ﺪﻧدﺮﻛ ﺰﺘﻨﺳ )
16 (.
ﻞﻜﺷ
1 تﺎﺒﻴﻛﺮﺗ ﻲﻳوراد تﺎﻘﺘﺸﻣ . ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛ
N N
Me O
Me Methaqualone
NH NH O S
Cl Me
O
O H2N
Quinethazone
NH N O
Me Cl
S O
O NH2
Metolazone
N N O
N N
N O
OH H
O
N N O
NH O
Luotonin A Cruciferane
Sclerotigenin
ود ﻲﺸﻫوﮋﭘ ﻲﻤﻠﻋ ﻪﻣﺎﻨﻫﺎﻣ دﺰﻳ ﺖﺷاﺪﻬﺑ عﻮﻠﻃ
لﺎﺳ و دادﺮﻣ، مﻮﺳ هرﺎﻤﺷ،ﻢﻫﺪﻔﻫ رﻮﻳﺮﻬﺷ
1397
شور لﻮﻤﻌﻣ ﺮﺗ ﺶﻨﻛاو ،تﺎﺒﻴﻛﺮﺗ ﻦﻳا ﺰﺘﻨﺳ ﻪﺳ
ﻲﺋﺰﺟ
ﻚﻴﺋﻮﺗاﺰﻳا
،ﺪﻳرﺪﻴﻧا ﻫﺪﻟآ و ﺪﻴ ﻣآ ﻦﻴ ﺎﻳ ﻚﻤﻧ ﻢﻴﻧﻮﻣآ ﺣ رد ﻀ رﻮ
ﻟﺎﺗﺎﻛ ﺖﺴﻴ يﺎﻫ ﺳا يﺪﻴ ﺖﺳا ) 17 ﻪﻛ(
ﻪﺘﺒﻟا ﻪﺑ ﻞﻴﻟد ﮔﺪﻧرﻮﺧ ﻲ و
ﻤﺳ ﺖﻴ ﻟﺎﺗﺎﻛ ﺖﺴﻴ يﺎﻫ ﺳا
،يﺪﻴ لﺎﺳ رد يﺎﻫ ﺧا ﺮﻴ ﻟﺎﺗﺎﻛ زا ﺖﺴﻴ يﺎﻫ
زﺎﺑ ي اﺮﺑ ي ﭘ دﺮﺒﺸﻴ ا ﻦﻳ ﺖﺳا هﺪﺷ هدﺎﻔﺘﺳا ﺶﻨﻛاو )
20 - 18 ( . ﺎﺑ
ﻪﺑ ﻪﺟﻮﺗ ﺴﻧﺎﺘﭘ ﻞﻴ وراد ﻲﻳ ﻛﺮﺗ تﺎﺒﻴ د ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ فﺪﻫ
ﻖﻴﻘﺤﺗ ﻦﻳا زا ﺰﺘﻨﺳ
تﺎﺒﻴﻛﺮﺗ ﻦﻳا رد
ﻂﻳاﺮﺷ ﺪﺟ ﺪﻳ ﻲﺳرﺮﺑ و و
ﻟﺎﻌﻓ ﺖﻴ ﺮﺘﻛﺎﺑ ﺪﺿ ﻲﻳﺎﻳ ﭼرﺎﻗ ﺪﺿ و ﻲ
نآ ﺎﻫ ﻲﻣ ﺪﺷﺎﺑ .
ﻲﺳرﺮﺑ شور
ﻘﺤﺗ ﻖﻴ يدﺎﻴﻨﺑ عﻮﻧ زا ﻲﺑﺮﺠﺗ -
يدﺮﺑرﺎﻛ سﺎﻴﻘﻣ رد ﻪﻛ ﺖﺳا
ﻲﻫﺎﮕﺸﻳﺎﻣزآ لﺎﺳ رد
1396 رد هﺎﮕﺸﻧاد دﺰﻳ .ﺪﺷ مﺎﺠﻧا
ﻠﻛ ﻪﻴ ﺷ داﻮﻣ ﻲﻳﺎﻴﻤﻴ ا رد هدﺎﻔﺘﺳا درﻮﻣ ﻦﻳ
ﻘﺤﺗ ﻖﻴ ﺖﻛﺮﺷ زا يﺎﻫ
ﺷ ﻲﻳﺎﻴﻤﻴ ﺳ و كﺮﻣ ﺎﻤﮕﻴ
- رﺪﻟا ﭻﻳ ﻬﺗ .ﺪﺷ ﻪﻴ ﺶﻨﻛاو تﺎﺤﻔﺻ ﺎﺑ ﺎﻫ
ﻣﻮﻟآTLC ﻲﻤﻴﻨﻴ راد ي ﺳ لژﺎﻜﻴﻠﻴ ﺮﮔﺎﺳﺎﻨﺷ و F245
60 .ﺪﺷ لﺎﺒﻧد
ﻃ ﻒﻴ NMR يﺎﻫ ﻚﻤﻛ ﻪﺑ ﻚﻳ
هﺎﮕﺘﺳد Bruker AV 500
لﻼﺣردMHz CDCl3يﺎﻫ
DMSO-d6ﺎﻳ ﻃ و
ﻒﻴ FT-يﺎﻫ
ﻧIR ﺰﻴ هﺎﮕﺘﺳد ﺎﺑ FT-IR
Bruker لﺪﻣ .ﺪﺷ ﺖﺒﺛ
تﺎﻘﺘﺸﻣ ﺰﺘﻨﺳ ياﺮﺑ رﺎﻛ شور 2
و 3 - د ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ
د تﺎﻘﺘﺸﻣ ﺰﺘﻨﺳ رﻮﻈﻨﻣ ﻪﺑ ي
،ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ ﺋﺰﺟ ﻪﺳ ﺶﻨﻛاو
ﻲ
ا ﻚﻴﺋﻮﺗاﺰﻳ ﻧا
ﺪﻳرﺪﻴ ) 1 ﻲﻠﻴﻣ لﻮﻣ ﻫﺪﻟآ ،(
ﺪﻴ ) 1 ﻲﻠﻴﻣ لﻮﻣ و ،(
ﻧﻮﻣآ ﻢﻴ - ) تﺎﺘﺳا 5 / 1 ﻲﻠﻴﻣ لﻮﻣ اﺮﺷ رد ( ﻂﻳ
ﻏ بﺎﻴ رد و لﻼﺣ
رﻮﻀﺣ ﻮﻧﺎﻧ ﻟﺎﺗﺎﻛ ﺖﺴﻴ ﻦﮕﻤﻫﺎﻧ يزﺎﺑ ﺰﻟﻮﻠﺳ )
01 / 0 مﺮﮔ هدﺎﻔﺘﺳا ﺎﺑ (
زا ﻳ ﺎﻣد رد نﺰﻤﻫ ﻚ ي
80 داﺮﮕﻴﺘﻧﺎﺳ ﻪﺟرد .ﺪﺷ مﺎﺠﻧا
ياﺮﺑ
لﻮﺼﺤﻣ يزﺎﺳاﺪﺟ ﺎﭘ رد
نﺎﻳ
،ﺶﻨﻛاو غاد نﻮﺘﺳا )
5 ﻲﻠﻴﻣ ﺮﺘﻴﻟ ﻪﺑ (
ﺤﻣ ﻂﻴ ﻪﻓﺎﺿا
، لﻮﺼﺤﻣ رد و ﻞﺣ نﻮﺘﺳا ﺗﺎﻛ زا
ﺎ ﻴﻟ ﺖﺴ شور ﻪﺑ
فﺎﺻ ﺶﻳاﺰﻓا ﺎﺑ .ﺪﺷ اﺪﺟ ندﺮﻛ دﺮﺳ بآ
) 5 ﻲﻠﻴﻣ ﺮﺘﻴﻟ ( لﻮﻠﺤﻣ ﻪﺑ لﻮﺼﺤﻣ نﻮﺘﺳا رد لﻮﺼﺤﻣ
ﺲﭘ بﻮﺳر ترﻮﺻ ﻪﺑ ﻒﻴﻗ ﺎﺑ و هدز
دﺮﺑرﺎﻛ زا نﺎﻨﻴﻤﻃا ياﺮﺑ ،ﻻﺎﺑ صﻮﻠﺧ دﻮﺟو ﺎﺑ .ﺪﺷ فﺎﺻ ﺮﻨﺧﻮﺑ زا لﻮﺼﺤﻣ ،ﻲﻳوراد لﻮﻧﺎﺗا و بآ
دﺪﺠﻣ رﻮﻠﺒﺗ .ﺪﺷ
و بوذ طﺎﻘﻧ
ا تﺎﺼﺨﺸﻣ ﻲﭘﻮﻜﺳوﺮﺘﻜﭙﺳ
وNMR FT-IR هﺪﺷﺰﺘﻨﺳ تﺎﻘﺘﺸﻣ
نآ رﺎﺘﺧﺎﺳ ًﻼﻣﺎﻛ ) دﺮﻛ ﺪﻴﻳﺎﺗ ار ﺎﻫ
20
، 19 .(
اﺮﺑ رﺎﻛ شور ي
ﺳرﺮﺑ ﻲ ﻟﺎﻌﻓ ﺖﻴ ﻣ ﺪﺿ ﻲﺑوﺮﻜﻴ
ﻟﺎﻌﻓ ﺖﻴ ﻣ ﺪﺿ ﻲﺑوﺮﻜﻴ رﺎﻬﭼ ﺮﻫ ياﺮﺑ د ﻖﺘﺸﻣ
ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ
ﺰﺘﻨﺳ ﺶﻫوﮋﭘ ﻦﻳا رد ي (1a-1d)
ﺎﺑ ﺎﻘﻣ ﻪﺴﻳ ﺮﺑ ﺶﻨﻜﻤﻫ
نآ ﺎﻫ ﺮﺑ ﻠﻋ ﻪﻴ ﺮﺘﻛﺎﺑ ي يﺎﻫ ﻨﻣ مﺮﮔ ـ ﻔ ﻲ ﺷﺮﺷا ﻠﻛﺎﻴ ـ (E-Coli) ﻲ
(ATTCC9144) ﮔ و
ــ ﺒﺜﻣ مﺮ ـ
ﺳﺎﺑ ﺖ ــ
ﻠﻴ ـ سﻮ
ﺘﺑﺎﺳ ﺲﻴﻠﻴ ATCC6051) وراد ﺎﺑ (
ي ﻣآ دراﺪﻧﺎﺘﺳا ﻦﻴﺳﺎﻜﻴ
) 25
(g/mL مﺎﺠﻧا ﺪﺑ .ﺪﺷ ﻦﻳ ﭘ رﻮﻈﻨﻣ ﺖﻠﻴ ﺎﻫ ي اﺮﺑ هﺪﺷ هدﺎﻣآ ي
ﺖﺴﺗ
ﻣ ﻲﺑوﺮﻜﻴ تﺪﻤﺑ 24 ﺎﻣد رد ﺖﻋﺎﺳ ي
37 داﺮﮕﻴﺘﻧﺎﺳ ﻪﺟرد راﺮﻗ
ﺮﻄﻗ و ﺖﻓﺮﮔ مﺪﻋ ﻪﻟﺎﻫ
ﺮﺑ ﺪﺷر ﺐﺴﺣ ﻲﻠﻴﻣ هزاﺪﻧا ﺮﺘﻣ ﮔ يﺮﻴ ﻪﺑ و
ﻌﻣ ناﻮﻨﻋ يرﺎﻴ زا ﺖﻴﻟﺎﻌﻓ ﺮﺘﻛﺎﺑ ﺪﺿ ﻲﻳﺎﻳ
.ﺪﺷ ﻪﺘﻓﺮﮔ ﺮﻈﻧ رد
ﻟﺎﻌﻓ ﺖﻴ ﺎﻫ ي ﭼرﺎﻗ ﺪﺿ ﻲ
ا ﻦﻳ ﻛﺮﺗ تﺎﺒﻴ ﺰﺘﻨﺳ ي ﻧ ﺰﻴ اﺮﺑ ي چرﺎﻗ
سﻮﻠﻳﮋﭙﺳآ ﺮﺠﻴﻧ
ATCC90290 ) ﺤﻣ رد (
ﻂﻴ ﺮﺘﺳا ﻞﻳ و رﺎﮔآ
د لﻼﺣ ي ﻞﻴﺘﻣ ﺪﻴﺴﻛﻮﻔﻟﻮﺳ DMSO )
( رد ﺖﻈﻠﻏ يﺎﻫ 25 و 50
ﻣ مﺮﮔوﺮﻜﻴ ﻣ رد
ﻲﻠﻴ ﺎﺑ ﺮﺘﻴﻟ لوزﺎﻧﻮﻛﻮﺘﻛ چرﺎﻗ ﺪﺿ ﻞﻣﺎﻋ لﻮﻠﺤﻣ و
ﻫﺎﺷ DMSO ﺪ ﻘﻣ ﻪﺴﻳﺎ .ﺪﺷ
،رﻮﻈﻨﻣ ﻦﻳا ﻪﺑ ﺮﺘﺳا زا ﺲﭘ
ﻞﻳ
ﺶﺨﭘ و بوذ رﺎﮔآ ندﺮﻛ
ﺖﺧاﻮﻨﻜﻳ د لﻮﻠﺤﻣ ،نآ
ي نﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ ﺎﻫ
DMSO رد
ﻣ ﻂﺳﻮﺗ ﺖﭙﻴﭘوﺮﻜﻴ ﺤﻣ ﻪﺑ
ﻂﻴ .ﺪﺷ ﻪﻓﺎﺿا
ﭘ ﺖﻠﻴ ﺎﻫ تﺪﻣ ﻪﺑ 24 ﺎﻣد رد ﺖﻋﺎﺳ ي
37 داﺮﮕﻴﺘﻧﺎﺳ ﻪﺟرد راﺮﻗ
ﺪﺷ هداد و ﺮﻄﻗ مﺪﻋ ﻪﻟﺎﻫ ﻢﻫ ﺎﺑ ﻪﻧﻮﻤﻧ رد ﺪﺷر دراﺪﻧﺎﺘﺳا ﻪﻧﻮﻤﻧ ﺎﺑ و
ﺎﻘﻣ ﻪﺴﻳ .ﺪﺷ
ود ﻲﺸﻫوﮋﭘ ﻲﻤﻠﻋ ﻪﻣﺎﻨﻫﺎﻣ دﺰﻳ ﺖﺷاﺪﻬﺑ عﻮﻠﻃ
لﺎﺳ رﻮﻳﺮﻬﺷ و دادﺮﻣ، مﻮﺳ هرﺎﻤﺷ،ﻢﻫﺪﻔﻫ 1397
ﺎﻫ ﻪﺘﻓﺎﻳ
تﺎﻘﺘﺸﻣ 2 و 3 - د ي رد هﺪﺷ ﻪﻳارا ﻲﻠﻛ شور ﻪﺑ ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ
ﻞﻜﺷ 2 و ﻪﻓﺎﺿا غاد نﻮﺘﺳا ،ﺶﻨﻛاو ﺮﻫ نﺎﻳﺎﭘ زا ﺲﭘ .ﺪﻧﺪﺷ ﺰﺘﻨﺳ
اﺰﻓا ﺎﺑ .ﺪﺷ اﺪﺟ لﻮﺼﺤﻣ زا ﺖﺴﻴﻟﺎﺗﺎﻛﻮﻧﺎﻧ لﻮﺼﺤﻣ دﺮﺳ بآ ﺶﻳ
ﻲﻟﺎﺘﺴﻳﺮﻛ ﻲﻜﻳﺰﻴﻓ و ﻲﭘﻮﻜﺳوﺮﺘﻜﭙﺳا تﺎﺼﺨﺸﻣ .ﺪﺷ فﺎﺻ ﺮﻨﺧﻮﺑ ﻒﻴﻗ ﺎﺑ
نآ رﺎﺘﺧﺎﺳ ﺎﺑ ًﻼﻣﺎﻛ هﺪﺷ ﺰﺘﻨﺳ تﺎﻘﺘﺸﻣ ﺖﺷاد ﻲﻳﺎﻧاﻮﺧ ﺎﻫ
) 20،19 .(
ﺪﺿ ﺖﻴﻟﺎﻌﻓ ﻪﺴﻳﺎﻘﻣ و ﻲﺳرﺮﺑ زا ﻞﺻﺎﺣ ﺞﻳﺎﺘﻧ ﻲﻳﺎﻳﺮﺘﻛﺎﺑ
تﺎﻘﺘﺸﻣ
يﺰﺘﻨﺳ 2 و 3 - د ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ دﺎﻘﻣ رد
ﺮﻳ 25 ﻣ مﺮﮔوﺮﻜﻴ ﺮﺑ
ور ي ﺮﺘﻛﺎﺑ ي يﺎﻫ ﻔﻨﻣ مﺮﮔ ﻲ ﺷﺮﺷا و ﻲﻠﻛﺎﻴ ﺳﺎﺑ ﺖﺒﺜﻣ مﺮﮔ -سﻮﻠﻴ
ﺲﻴﻠﺘﺑﻮﺳ ﺎﺑ
وراد ي ﻣآ شور ﻪﺑ ﻦﻴﺳﺎﻜﻴ د نﻮﻣزآ
ﻚﺴﻳ د ﺎﺑ نژﻮﻴﻔﻳ
هزاﺪﻧا ﺪﺷر مﺪﻋ ﻪﻟﺎﻫ يﺮﻴﮔ لوﺪﺟ رد
1 .ﺖﺳا هﺪﺷ شراﺰﮔ
ﻟﺎﻌﻓ نﻮﻣزآ ﺖﻴ
¬ﺪﺿ ﻲﭼرﺎﻗ تﺎﻘﺘﺸﻣ ﺮﻳدﺎﻘﻣ رد يﺰﺘﻨﺳ 25
و 50
مﺮﮔوﺮﻜﻴﻣ ور ﺮﺑ
ي ژﺮﭙﺳآ چرﺎﻗ سﻮﻠﻳ
ﺮﺠﻴﻧ ﺎﻘﻣ رد ﻪﺴﻳ ﺎﺑ وراد ي
دراﺪﻧﺎﺘﺳا د نﻮﻣزآ ﻂﺳﻮﺗ لوزﺎﻧﻮﻛﻮﺘﻛ
ﻚﺴﻳ د نژﻮﻴﻔﻳ هزاﺪﻧا ﺎﺑ
ﮔ يﺮﻴ ﺪﺷر مﺪﻋ ﻪﻟﺎﻫ يﺎﻣد رد
37 ﺞﻳﺎﺘﻧ و مﺎﺠﻧا داﺮﮕﻴﺘﻧﺎﺳ ﻪﺟرد
نآ لوﺪﺟ رد 2
.ﺖﺳا هﺪﺷ شراﺰﮔ
سﺎﺳا ﺮﺑ ﺎﺘﻧ
،ﺞﻳ ﻛﺮﺗ ﺐﻴ 2 - ﻨﻓ ﻞﻴ - 2 و 3 - د ي ﻦﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ -
4 -
H) ( - نوا 1d ) ( سﺎﻴﻘﻣ رد يﺎﻫ
25 و 50 ﻣ مﺮﮔوﺮﻜﻴ ﻟﺎﻌﻓ
ﺖﻴ
ﺪﺿ ﻲﭼرﺎﻗ ز يﺮﺗدﺎﻳ ﺶﻳﺎﻣزآ درﻮﻣ تﺎﻘﺘﺸﻣ ﺮﻳﺎﺳ ﻪﺑ ﺖﺒﺴﻧ زا
دﻮﺧ .ﺖﺳا هداد نﺎﺸﻧ
ﻞﻜﺷ
2 . ﻣﻮﻤﻋ شور ﻲ
تﺎﻘﺘﺸﻣ ﺰﺘﻨﺳ 2
و 3 - د ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ
لوﺪﺟ 1 نﻮﻣزآ ﺞﻳﺎﺘﻧ : ﻲﻳﺎﻳﺮﺘﻛﺎﺑ ﺪﺿ ﺖﻴﻟﺎﻌﻓ
تﺎﻘﺘﺸﻣ يﺰﺘﻨﺳ 2 و 3 - د ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ ور ﺮﺑ
ي ﺮﺘﻛﺎﺑ ي يﺎﻫ ﺷﺮﺷا و ﻲﻠﻛﺎﻴ ﺳﺎﺑ سﻮﻠﻴ
ﺲﻴﻠﺘﺑﻮﺳ ﻂﺳﻮﺗ د نﻮﻣزآ ﻚﺴﻳ د نژﻮﻴﻔﻳ
ﻒﻳدر د تﺎﻘﺘﺸﻣ
¬ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ ﺰﺘﻨﺳ
ي ﻲﻠﻛﺎﻴﺷﺮﺷا يﺮﺘﻛﺎﺑ ﺪﺷر مﺪﻋ ﻪﻟﺎﻫ ﺮﻄﻗ
ﻲﻠﻴﻣ) (ﺮﺘﻣ ﺮﻄﻗ
مﺪﻋ ﻪﻟﺎﻫ سﻮﻠﻴﺳﺎﺑ يﺮﺘﻛﺎﺑ ﺪﺷر ﺲﻴﻠﻴﺘﺑﻮﺳ
ﻲﻠﻴﻣ) (ﺮﺘﻣ
1 1a
3 3
2 1b
3 6
3 1c
3 5
4 1d
4 9
5 ﻦﻴﺳﺎﻜﻴﻣآ
16 19
ود ﻲﺸﻫوﮋﭘ ﻲﻤﻠﻋ ﻪﻣﺎﻨﻫﺎﻣ دﺰﻳ ﺖﺷاﺪﻬﺑ عﻮﻠﻃ
لﺎﺳ و دادﺮﻣ، مﻮﺳ هرﺎﻤﺷ،ﻢﻫﺪﻔﻫ رﻮﻳﺮﻬﺷ
1397
ﻣ مﺮﮔوﺮﻜﻴ µg)
(
در ﻒﻳ ﻛﺮﺗ ﺐﻴ مﺪﻋ ﻪﻟﺎﻫ ﺮﻄﻗ
ژﺮﭙﺳآ ﺪﺷر سﻮﻠﻳ
ﻧ ﺮﺠﻴ ﻣ) ﻲﻠﻴ (ﺮﺘﻣ ژﺮﭙﺳآ ﺪﺷر مﺪﻋ ﻪﻟﺎﻫ ﺮﻄﻗ
سﻮﻠﻳ ﻧ ﺮﺠﻴ ﻣ) ﻲﻠﻴ (ﺮﺘﻣ
ﻣ25 مﺮﮔوﺮﻜﻴ ﻣ50
مﺮﮔوﺮﻜﻴ
1 1a
- 3
2 1b
3 6
3 1c
3 5
4 1d
4 12
5 لوزﺎﻧﻮﻛﻮﺘﻛ ياﺮﺑ
10 µg ﺎﺑ ﺮﺑاﺮﺑ 16 -
ﺘﻧ و ﺚﺤﺑ ﻪﺠﻴ
ﮔ يﺮﻴ
فﺪﻫ نﻮﭼ ا
ﻦﻳ ﻘﺤﺗ ﻖﻴ و ﺰﺘﻨﺳ ﺳرﺮﺑ ﻲ ﻟﺎﻌﻓ ﺖﻴ ﺪﺿ ﭼرﺎﻗ ﻲ -ﺪﺿ و
ﺑ ﺮﺘﻛﺎ ﻲﻳﺎﻳ ﻛﺮﺗ تﺎﺒﻴ ﺳوﺮﺘﻫ ﻞﻜﻴ 2 و 3 - د ي ﻫ ورﺪﻴ ﻛ ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴ رد
يﺰﻟﻮﻠﺳ يزﺎﺑ ﺖﺴﻴﻟﺎﺗﺎﻛﻮﻧﺎﻧ رﻮﻀﺣ ﺪﺟ
ﺪﻳ دﻮﺑ ﻖﺘﺸﻣ رﺎﻬﭼ اﺪﺘﺑا ،
تﺎﻘﺘﺸﻣ ﺎﻳ ﺪﻴﻫﺪﻟاﺰﻨﺑ ﺶﻨﻛاو زا تﺎﺒﻴﻛﺮﺗ ﻦﻳا زا 4
- ،ﻮﻣﺮﺑ 4 - وﺮﻠﻛ
و 4 - ﺎﺑ نآ ﻲﺴﻛورﺪﻴﻫ ا
ﻚﻴﺋﻮﺗاﺰﻳ ﻧا
ﺪﻳرﺪﻴ ﻧﻮﻣآ و ﻢﻴ تﺎﺘﺳا ﻪﺑ
هدزﺎﺑ ًﻻوا ﻪﻛ داد نﺎﺸﻧ ﺞﻳﺎﺘﻧ .ﺪﻧﺪﺷ ﺰﺘﻨﺳ ﻲﺑﺮﺠﺗ شور شور زا ﺮﺘﺸﻴﺑ شور ﻦﻳا رد تﻻﻮﺼﺤﻣ ًﺎﻴﻧﺎﺛ و ﺖﺳا ﻲﻠﺒﻗ يﺎﻫ
ﻲﺘﺣ ﻪﻛ يرﻮﻃ ﻪﺑ دﻮﺑ دﺎﻳز رﺎﻴﺴﺑ يﺰﺘﻨﺳ تﻻﻮﺼﺤﻣ صﻮﻠﺧ بآ زا هﺪﺸﻧ رﻮﻠﺑﻮﻧ تﻻﻮﺼﺤﻣ -
و ﻲﻜﻳﺰﻴﻓ صاﻮﺧ ﻢﻫ لﻮﻧﺎﺗا
ﺪﻧداد نﺎﺸﻧ ار دﻮﺧ رﺎﺘﺧﺎﺳ ﺮﺑ ﻖﺒﻄﻨﻣ ﻲﭘﻮﻜﺳوﺮﺘﻜﭙﺳا )
20
، 19 .(
،ﺪﻌﺑ ﻪﻠﺣﺮﻣ رد ﻟﺎﻌﻓ نﻮﻣزآ
ﺖﻴ ﺪﺿ ﺮﺘﻛﺎﺑ ﻲﻳﺎﻳ ياﺮﺑ تﺎﻘﺘﺸﻣ
ﺰﺘﻨﺳ ي 2 و 3 - د
¬ي و مﺎﺠﻧا ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ ﺪﺷ ﺺﺨﺸﻣ
ﻪﻛ
ﻬﭼ ﺮﻫ ﺎ ﻛﺮﺗ ر ﺐﻴ ﺰﺘﻨﺳ ي ﻟﺎﻌﻓ ﺖﻴ ﺮﺘﻛﺎﺑ ﺪﺿ يﺮﺘﻛﺎﺑ ود ﻪﻴﻠﻋ ﻲﻳﺎﻳ
لوﺪﺟ) ﺪﻧراد ﻲﻔﻨﻣ مﺮﮔ و ﺖﺒﺜﻣ مﺮﮔ 1
.(
ﺎﺘﻧ ﺞﻳ ﻪﻠﺻﺎﺣ نﺎﺸﻧ
ﻲﻣ ﻪﻛ ﺪﻫد ﻣ زا نﺎﻴ تﺎﻘﺘﺸﻣ د ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ هﺪﺷ ﻪﺴﻳﺎﻘﻣ
،ﻦﻴﺳﺎﻜﻴﻣآ دراﺪﻧﺎﺘﺳا يوراد ﺎﺑ ﻛﺮﺗ
ﺐﻴ 2 - ﻨﻓ ﻞﻴ - 2 و 3 - د -ي
ﻦﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ -
4 - H) ( - نوا 1d) ( ﻟﺎﻌﻓ ﻴـ ﺖ ﺪﺿ ﻛﺎﺑ ـ ﻲﻳﺎﻳﺮﺘ
ز يﺮﺗدﺎﻳ ﺖﻴﻟﺎﻌﻓ ﺶﻳاﺰﻓا ﻦﻳا .ﺖﺳا هداد نﺎﺸﻧ دﻮﺧ زا ﻪﻴﻠﻋ
ﺮﺘﻛﺎﺑ ي ﺳﺎﺑ ﺖﺒﺜﻣ مﺮﮔ سﻮﻠﻴ
ﺘﺑﻮﺳ ﺲﻴﻠﻴ ﺐﻴﻛﺮﺗ ياﺮﺑ 1d
.ﺖﺳا ﺮﺗﺮﻴﮕﻤﺸﭼ ﻟﺎﻌﻓ و رﺎﺘﺧﺎﺳ طﺎﺒﺗرا ﻪﺑ ﻪﺟﻮﺗ ﺎﺑ
ﺖﻴ ﺑ ﻲﻜﻳژﻮﻟﻮﻴ
لﻮﻜﻠﻣ يﺎﻫ ﺖﻤﺴﻗ ﺮﻳﺎﺳ ندﻮﺑ كﺮﺘﺸﻣ و 1a-1dيﺎﻫ
، ﺑ ﺮﻈﻧ ﻪ
ﻲﻣ عﻮﻧ ﻪﻛ ﺪﺳر ﻫوﺮﮔ
ﻲ ﻌﻗﻮﻣ رد ﻪﻛ ﺖﻴ
2 ﻪﻘﻠﺣ ﻲﻨﻴﻟوزﺎﻨﻴﻛ راﺮﻗ
ﻣ دﺮﻴﮔ ﻲ ﻟﺎﻌﻓ ﺮﺑ تﺪﺷ ﻪﺑ
ﺖﻴ ﺐﻴﻛﺮﺗ د ي ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ
ﺛﺎﺗ ﺮﻴ ﺖﺳا راﺬﮔ .
نﻮﻣزآ زا ﻞﺻﺎﺣ ﺞﻳﺎﺘﻧ ﻟﺎﻌﻓ
ﺖﻴ ﺪﺿ ﻲﭼرﺎﻗ تﺎﻘﺘﺸﻣ يﺰﺘﻨﺳ 1a-
ﺮﻳدﺎﻘﻣ رد 1d 25
و 50 ﻪﻴﻠﻋ مﺮﮔوﺮﻜﻴﻣ ژﺮﭙﺳآ چرﺎﻗ
سﻮﻠﻳ ﺮﺠﻴﻧ
رد ﺎﻘﻣ ﻪﺴﻳ وراد ﺎﺑ ي دراﺪﻧﺎﺘﺳا لوزﺎﻧﻮﻛﻮﺘﻛ
لوﺪﺟ رد ﻪﻛ 2
ﻲﻣ نﺎﺸﻧ هﺪﺷ ﻪﺻﻼﺧ ﺪﺿ ﺖﻴﻟﺎﻌﻓ ﺐﻴﻛﺮﺗ رﺎﻬﭼ ﺮﻫ ﻪﻛﺪﻫد
ﺐﻴﻛﺮﺗ ﻲﭼرﺎﻗ ﺪﺿ ﺖﻴﻟﺎﻌﻓ ﻪﭼ ﺮﮔا ،ﺪﻧراد ﻲﭼرﺎﻗ ﻪﻴﻘﺑ زا 1d
.ﺖﺳا ﺮﺘﺸﻴﺑ تﺎﻘﺘﺸﻣ ا ﺖﻠﻋ
ﻦﻳ ﻟﺎﻌﻓ ﺖﻴ ﺑ ﺮﺘﺸﻴ ﻣ ﻲ ﻪﺑ طﻮﺑﺮﻣ ﺪﻧاﻮﺗ
ﻮﺟو د ﺮﮔ بآ هوﺮﮔ ﺰﻳ
ﻨﻓ ﻞﻴ ﻌﻗﻮﻣ رد ﺖﻴ
2 ﻪﻘﻠﺣ
يد ورﺪﻴﻫ ﻛ ﺐﻴﻛﺮﺗ ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴ .ﺪﺷﺎﺑ 1d
ﺐﻴﻛﺮﺗ ﺰﻴﭼﺎﻧ ﺖﻴﻟﺎﻌﻓ
ﺖﺳوﺪﺑآ 1aﺮﺗ
يارﺎﭘ ﺖﻴﻌﻗﻮﻣ رد ﻲﺴﻛورﺪﻴﻫ هوﺮﮔ ياراد ﻪﻛ
.ﺖﺳﺎﻋدا ﻦﻳا ﺮﺑ ﻲﺘﺤﺻ ﺖﺳا ﻪﻘﻠﺣ
ﺧ ـ ﺿ صاﻮ ـ
ﻗ ﺪ ـ ﭼرﺎ ـ ﻲ و ﺿ ـ ﺘﻛﺎﺑ ﺪ ـ ﺮ ﻲﻳﺎﻳ ﺒﺜﻣ ــ ﺖ
د
¬ي نﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ يﺎﻫ
ﻪﺑﺎﺸﻣ ﺎﺘﺒﺴﻧ ﺰﺘﻨﺳ
هﺪﺷ ﻧاﺮﺘﻧآ زا ﻦﻴﻠﻴ
ﻣآ ﺪﻴ و ﺋﺪﻟآ ﻂﺳﻮﺗ ﺎﻫﺪﻴ Vasudhevan
Karunakaran و رد
ود ﻲﺸﻫوﮋﭘ ﻲﻤﻠﻋ ﻪﻣﺎﻨﻫﺎﻣ دﺰﻳ ﺖﺷاﺪﻬﺑ عﻮﻠﻃ
لﺎﺳ رﻮﻳﺮﻬﺷ و دادﺮﻣ، مﻮﺳ هرﺎﻤﺷ،ﻢﻫﺪﻔﻫ 1397
لﺎﺳ 2013 ور ي ﺪﻧﺎﻛ ﺲﻧاﺪﻳ ﺒﻟآ ﺲﻨﻜﻴ ژﺮﭙﺳآ و سﻮﻠﻳ ﺎﻧ ﺮﺠﻳ ﺎﺑ
ﺎﺘﻧ ﺞﻳ ا ﻦﻳ ﻘﺤﺗ ﻖﻴ ﻫ ﻢ ﻲﻧاﻮﺧ دراد ) 6 ( .
ﺧ ـ ﺿ صاﻮ ـ
ﺮﺘﻛﺎﺑ ﺪ ﻳـ
ﮔ ﻲﻳﺎ ــ ﺷ شراﺰ ــ
ﺑ هﺪ ـ ياﺮ
د
¬ي نﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪﻴﻫ يﺎﻫ
زا هﺪﺷ ﺰﺘﻨﺳ يد
ﻫ ورﺪﻴ ﺑآ ﻦﻴﻣﻶﻴﺘﻴ
DHA) (
، ا ﻚﻴﺋﻮﺗاﺰﻳ ﻧا
ﺪﻳرﺪﻴ ﺋﺪﻟآو ﺎﻫﺪﻴ ﻂﺳﻮﺗ ﻲﺤﻟﺎﺻ و
لﺎﺳ رد نارﺎﻜﻤﻫ 2014
ﺮﺑ يﺪﻴﻳﺎﺗ ﺰﻴﻧ ﺎﺘﻧ
ﺞﻳ ا ﻦﻳ ﻘﺤﺗ ﻖﻴ
ﺖﺳا ) 21 .(
شراﺰﮔ ﺪﺿ صاﻮﺧ ﻲﻳﺎﻳﺮﺘﻛﺎﺑ
ﻲﻠﻛﺎﻴﺷﺮﺷا يﺮﺘﻛﺎﺑ ﻪﻴﻠﻋ ياﺮﺑ
ﺘﺸﻣ ـ توﺎﻔﺘﻣ تﺎﻘ د
ي ﻴﻫ ـ ﻨﺳ ﻲﻧﻮﻨﻴﻟوزﺎﻨﻴﻛورﺪ ـ
ﺷ ﺰﺘ ـ زا هﺪ
ﺋﻮﺗاﺰﻳا ـ ﻂﺳﻮﺗ ﻦﻴﺗاﺰﻳا و ﻦﻴﻠﻴﻧآ ،ﺪﻳرﺪﻴﻧا ﻚﻴ Zhang
ﻤﻫ و ـ نارﺎﻜ لﺎﺳ رد
2016 ﻲﻣ ﺖﺑﺎﺛ ار ﺪﻴﻳﺎﺗ ﻖﻴﻘﺤﺗ ﻦﻳا ﺞﻳﺎﺘﻧ ﻢﻫ ) ﺪﻨﻛ
22 .(
ﻊﻓﺎﻨﻣ دﺎﻀﺗ
ﻲﻌﻓﺎﻨﻣ دﺎﻀﺗ ﻪﻧﻮﮔ ﭻﻴﻫ ﺪﻧراد ﻲﻣ مﻼﻋا ﻪﻟﺎﻘﻣ ﻦﻳا نﺎﮔﺪﻨﺴﻳﻮﻧ .دراﺪﻧ دﻮﺟو
ﻲﻧادرﺪﻗ و ﺮﻜﺸﺗ
و هﺪﺷ مﺎﺠﻧا دﺰﻳ هﺎﮕﺸﻧاد ﻲﻤﻴﺷ هﺪﻜﺸﻧاد ﺖﻳﺎﻤﺣ ﺎﺑ ﺶﻫوﮋﭘ ﻦﻳا تﺪﻋﺎﺴﻣ زا ﻪﻠﻴﺳﻮﻨﻳﺪﺑ ﻲﻣ يراﺰﮕﺳﺎﭙﺳ هﺎﮕﺸﻧاد ﻦﻳا يﺎﻫ
.دﻮﺷ
يرﺎﻜﻤﻫ زا ﻦﻴﻨﭽﻤﻫ ﻘﺤﺗ ﺰﻛﺮﻣ
تﺎﻘﻴ ﺳﺪﻨﻬﻣ ﻲ ﺤﻣ ﺖﺷاﺪﻬﺑ ﻂﻴ
مﻮﻠﻋ هﺎﮕﺸﻧاد ﻜﺷﺰﭘ
ﻲ نﺎﻣﺮﻛ و ﻣﻼﺳا دازآ هﺎﮕﺸﻧاد ﻲ
ﺪﺣاو دﺰﻳ
ﻲﻣ يراﺰﮕﺳﺎﭙﺳ ﻖﻴﻘﺤﺗ ﻦﻳا مﺎﺠﻧا ياﺮﺑ نﺎﻧآ .دﻮﺷ
References
1-Okumura K, Oine T, Yamada Y, Hayashi G, Nakama M.4-Oxo-1,2,3,4-tetrahydroquinazolines. I.
Syntheses and pharmacological properties of 2-methyl-3-aryl-4-oxo-1,2,3,4-tetrahydroquinazolines and their 1-acyl derivatives. Journal of Medicinal Chemistry. 1968;11(2):348–52.
2-Bonola G, Da Re P, Magistretti MJ, Massarani E, Setnikar I.1-Aminoacyl-2,3-dihydro-4(1H)- quinazolinone derivatives with choleretic and antifibrillatory activity. Journal of Medicinal Chemistry. 1968;11(6):1136–9.
3-Alaimo RJ, Russel HE.Antibacterial 2,3-dihydro-2-(5-nitro-2-thienyl)-quinazolin-4(1H)-ones.
Journal of Medicinal Chemistry. 1972;15(3):335–6.
4-Neil GL, Li LH, Buskirk, HH, Moxley TE.Antitumor effects of the antispermatogenic agent, 2,3- dihydro-2-(1-naphthyl)-4(1H)-quinazolinone.
Cancer Chemotherapy Pharmacology. 1972;56(2):163–8.
5-Levin JI .2,3,6–Substituted quinazolinones as angiotensin II receptor antagonists. Bioorganic &
Medicinal Chemistry Letters. 1994;4 (3):1141–6.
6-Vasudhevan S, Karunakaran RJ, Synthesis.Characterisation of 2,3-Dihydroquinazolinone Derivatives and their Antimicrobial Studies. International Journal of Chem Tech Research, 2013;5(6):2844-53.
ود ﻲﺸﻫوﮋﭘ ﻲﻤﻠﻋ ﻪﻣﺎﻨﻫﺎﻣ دﺰﻳ ﺖﺷاﺪﻬﺑ عﻮﻠﻃ
لﺎﺳ و دادﺮﻣ، مﻮﺳ هرﺎﻤﺷ،ﻢﻫﺪﻔﻫ رﻮﻳﺮﻬﺷ
1397
Sc(OTf)3-catalyzed intramolecular amidation of imines. Journal of Fluorine Chemistry. 2015;169 (5):72–7.
8-Connolly DJ, Cusack D, OSullivan TP, Guiry PJ. Synthesis of Quinazolinones and Quinazolines.
Tetrahedron. 2005;61(2): 10153-202.
9-Zhongze M, Yoshio H, Taro N, A Lead toward Anti-Cancer Agent Development. Heterocycles.
2005;65(9):2203-19.
10-Sharma SD, Kaur V.Synthesis of 3-oxa-and 3-aza-1-dethiacepham analogs. Synthesis.
1989;9:677–680.
11-Rostamizadeh S, Nojavan M, Aryan R, Isapor E, Azad M.Amino acid-based ionic liquid immobilized on α-Fe2O3-MCM-41:An efficient magnetic nanocatalyst and recyclable reaction media for the synthesis of quinazolin. Synthetic Communications. 2008;38(20): 3567–76.
12-Chen J, Wu D, He F, Liu M, Wu H, Ding J, Su W.Gallium(III)triflate–catalyzed one-pot selective synthesis of 2,3-dihydroquinazolin-4(1H)-ones and quinazolin-4(3H)-ones. Tetrahedron Letter. 2008;49;3814–18.
13-Wang LM, Hu L, HuaShao J, Yu J, Zhang L.A Novel Catalyst Zinc (II) Perfluorooctanoate [Zn(PFO)2]-Catalyzed Three-Component One-Pot Reaction: Synthesis of Quinazoline Derivatives in Aqueous Micellar Media. Journal of Fluorine Chemistry. 2008;129: 1139–45.
14-Bunce RA, Nammalwar B.4 (1H)-Quinolinones by a tandem reduction-addition-elimination reaction J. Heterocyclic Chemistry. 2011; 48(3):991–7.
15-Ramesh K, Karnakar K, Satish G, Kumar BSPA, Nageswar YVDA.concise aqueous phase supramolecular synthesis of 2-phenyl-2,3-dihydroquinazolin-4(1H)-one derivatives. Tetrahedron Letter. 2012;53(51):6936–9.
16 -Wu X, Oschatz S, Block A, Spannenbergb A, Langer P.Base mediated synthesis of 2-aryl-2,3- dihydroquinazolin-4(1H)-ones from 2-aminobenzonitriles and aromatic aldehydes in water. Organic
& Biomolecular Chemistry. 2014;12(12):1865–70.
17-Abbas SY, El-Bayouki KAM, Basyouni WM.Utilization of isatoic anhydride in the syntheses of various types of quinazoline and quinazolinone derivatives. Synthetic Communications Reviews.
2016;46(12); 993-1035.
ود ﻲﺸﻫوﮋﭘ ﻲﻤﻠﻋ ﻪﻣﺎﻨﻫﺎﻣ دﺰﻳ ﺖﺷاﺪﻬﺑ عﻮﻠﻃ
لﺎﺳ رﻮﻳﺮﻬﺷ و دادﺮﻣ، مﻮﺳ هرﺎﻤﺷ،ﻢﻫﺪﻔﻫ 1397
18-Patil YP, Tambade PJ, Parghi KD, Jayaram RV, Bhanage BM.Synthesis of Quinazoline- 2,4(1H,3H)-Diones from Carbon dioxide and 2-Aminobenzonitriles Using MgO/ZrO2 as a Solid Base Catalyst. Catalysis Letters. 2009;133(1–2):201–8.
19-Tamaddon F, KazemiVarnamkhasti M.Scalable preparation, characterization, and application of alkali-treated starch as a new organic base catalyst. Carbohydrate Research. 2017;437: 9-15.
20-Tamaddon F, Pouramini F.Amberlyst A26OH as a recyclable catalyst for hydration of nitriles and water-based synthesis of 4(1 H)-quinazolinones from 2-aminobenzonitrile and carbonyl compounds. Synlett, 2014;25(8):1127-31.
21-Salehi P, Ayyari M, Bararjanian M, Nejad Ebrahimi S, Aliahmadi A.Synthesis, antibacterial and antioxidant activity of novel 2,3-dihydroquinazolin-4(1H)-one derivatives of dehydroabietylamine diterpene. Journal of the Iranian Chemical Society, 2014:(11):607–13.
22- Zhang J, Zhao J, Wang L, Liu J, Ren D, Ma Y.Design synthesis and docking studies of some spiro-oxindole dihydroquinazolinones as antibacterial agents. Tetrahedron, 2016;(72):936-43.
