Department of Biochemistry

Permanent URI for this collection

Browse

Recent Submissions

Now showing 1 - 5 of 12
  • Item
    Assessment of Bone Morphogenetic Proteins and BMPR1, BMPR2 Polymorphism in Simple Fractures among Sudanese Patients in Selected Khartoum Hospitals
    (University of Khartoum, 2020) Amin Ahmed Babiker Mohamed Ali
    Abstract Background: Bone morphogenetic proteins (BMP) are multifunctional proteins. They work as cytokines regulating osteogenesis. Controversies were present in recent studies on their therapeutic role. This study was designed to assess the effect of these proteins on bone fracture healing, and to identify polymorphisms in bone morphogenetic receptor 1 and 2. Methods: Case-Control study conducted from January 2018 to January 2019 in five hospitals in Khartoum state. Seventy-six patients and Seventy-six controls were consented and enrolled in the study. Participants aged from 18 to 65 years. Plasma concentrations TGFβ1, BMP-2, BMP-7, BMP-2/7, BMP-10 and vitamin D were measured using quantitative (ELISA) and Protein pull-down assays. BMPR1A and BMPR2 PCR products were digested by selected restriction enzymes. PCR products were also sent for DNA sequencing. SPSS ver.25 was used to calculate frequencies, Pearson correlation tests, and unpaired t-test. Odd ratio by MedCalac software. P <0.05 was considered statistically significant. Results: Seventy-six patients with fractures and Seventy-six controls were studied. Means of plasma concentrations were (BMP-2= 71.4 pg/ml ± 22 and 53.8 ng/ml ± 23) (BMP-7 = 13pg/ml ±0.5 and 62.5pg/ml ±45) (BMP2/7= 266.4 pg/ml ± 45.5 and 470 pg/ml± 49) (vitamin D mean was 24.94 ng/ml ±13.2 and 26.2 ng/ml ±11.6) in patients and controls, respectively. Fifty-seven patients completed the follow up (39 males, 18 females). 25% had BMPR1A [A] variant, while 100% had BMPR2 [A] variant. Significantly lower BMP-7 and BMP-2/7 heterodimer was present among patients (P= 0.042 and 0.021). BMP-7 was significantly correlated with time of presentation (P= 0.007). Fracture healing time was not significantly different between patients and controls (OR= 1.05, CI= 95%, P= 0.093), or between BMPR1 variant [T] or variant [A] (t= 0.36, P= 0.72). Conclusions: BMP-2/7 heterodimer was more abundant than homodimer. Healing time was influenced by BMP-7. In addition, low BMP-7 may have a role in fracture healing physiology. BMPR1A and BMPR2 polymorphisms may have a role on fracture healing. Majority of subjects under study have Vitamin D insufficiency. خلاصة خلفية: البروتينات المكونة للعظم لها عدة وظائف. فهي تعمل كسيتوكينات لتحفيذ عملية تكون العظام. مؤخرا تضاربت الدراسات في نتائجها بخصوص فاعلية هذه البروتينات في علاج الكسور. صممت هذه الدراسة لاستكشاف العوامل الكيميوحيوية لالتئام كسور العظام البسيطة, ذلك بغرض معرفة البروتينات المهمة لالتئام الكسور و دراسة التنوع الجيني لبوابات البروتين من النوع الاول و الثاني. طرائق البحث: دراسة حالات و شواهد استمرت منذ يناير 2018 حتي يناير 2019 في خمس مستشفيات بولاية الخرطوم. تم اخذ البيانات الديموغرافية و قياسات الجسم بالاضافة لضغط الدم كما تم اخذ عينات دم من الحالات و الشواهد ذوي اعمار من 18 سنة حتي 65 سنة. تم حساب تراكيز البروتينات المكونة للعظم و فيتامين (د) بواسطة مُقَايَسَةُ المُمْتَزِّ المَناعِيِّ المُرْتَبِطِ بالإِنْزِيْم. تم عمل تفاعل سلسلة البوليميرات و تَعَدُّدُ أَشْكَالِ أَطْوالِ الشُّدَفِ المُقْتَطَعَة لجينات البوابات من النوع الاول و الثاني لاستقبال البروتين المكون للعظم. كما أُرسلت نتائج التفاعل لمعرفة تسلسل الحمض النووي. تم استخدام النسخة الخامسة و العشرون من برنامج الإحصاء للعلوم الاجتماعية لحساب التردد و معامل ارتباط بيرسون و اختبار (تي) غير المقترن و نسبة الأرجحية. القيمة الاحتمالية أقل من 0.05 تعني إرتباط له دلالته الإحصائية. النتائج: اشتملت الدراسة علي ستة و سبعين مصابا بكسر بسيط و ستة و سبعين من الافراد الأصحاء بغرض المقارنة. متوسط تراكيز البلازما عند الحالات و الشواهد علي التوالي كانت كالاتي (BMP-2= 71.4 pg/ml ± 22| 53.8 ng/ml ± 23) (BMP-7 = 13pg/ml ±0.5 |62.5pg/ml ±45) (BMP2/7= 266.4 pg/ml ± 45.5 |470 pg/ml± 49) (Vitamin D mean was 24.94 ng/ml ±13.2 |26.2 ng/ml ±11.6) و تمت متابعة سبع و خمسين حالة حتي التئام الكسور: تسع و ثلاثون رجلا و ثمانية عشر امرأة. لم توجد أي علاقة بين البروتينات المكونة للعظم من النوع الثاني و السابع في شكل مَثْنَوِيٌّ مُغَايرمع زمن التئام الكسور. كان لدي 25% من الحالات المتغاير (أ) في جين البوابة الأول بينما 100% كان لديهم المتغاير (أ) في جين البوابة الثاني. البروتين المكون للعظم من النوع السابع و المَثْنَوِيٌّ المُغَاير كانوا أقل في الحالت مقارنة بالشواهد (القيمة الاحتمالية 0.042 و 0.021). النوع السابع كان له ارتباط وثيق مع زمن أخذ العينة (P= 0.007). بالنسبة لزمن التئام الكسور, لم يوجد فرق بين الحالات و الشواهد OR = 1.05, CI = 95%, P = 0.093)) ,أو بين المتغاير (أ) و المتغاير (تي) لجين بوابة البروتين من النوع الأول (t= 0.36, P= 0.72). الاستنتاجات :تواجد البروتينات المكونة للعظم من النوع الثاني و السابع في شكل مَثْنَوِيٌّ مُغَاير اكثر من التواجد الفردي. انخفاض تركيز البروتين من النوع السابع قد يكون له علاقة مع عملية التئام الكسور. التنوع الجيني في بوابات البروتين من النوع الاول و الثاني قد تؤثر علي وظيفه البروتينات المكونة للعظم. معظم المتطوعين لديهم نقص في فيتامين (د).
  • Item
    Larvicidal Activity of Essential oils from Nigella sativa L. and Pulicaria undulata (L.) C.A. Mey. against the Mosquito Vectors Anopheles gambiae and Culex quinquefasciatus
    (University of Khartoum, 2020-11) Hind Fadlalmoola Mohammed Mansour
    Abstract The use of chemical insecticides for controlling mosquitoes have not only resulted in development of resistance in mosquito strains but have also caused environmental pollution and the death of non-target organisms including beneficial organisms such as honeybees and fish. This has stimulated the investigation of ecofriendly natural insecticides as an alternative control. This study aimed at the possible use of essential oils extracted from Nigella sativa seeds and Pulicaria undulata whole plant against the mosquito vectors Anopheles gambiae and Culex quinquefasciatus. Seeds of N. sativa were purchased from the local market in Khartoum. Pulicaria undulata was collected from Alhalfaia, Khartoum North, Sudan. Essential oils from the dried plant materials were obtained by hydrodistillation. Phytochemical analysis of essential oils was performed by thin layer chromatography (TLC) and gas chromatography coupled with mass spectrometry (GC–MS) techniques. Different concentrations; 0.2%, 0.4%, 0.6%, 0.8% and 1.0% of each essential oils were prepared for the larvicidal assay. Third instar larvae of An. gambiae and Cx quinquefasciatus were provided by Soba Malaria Researches Laboratory in October 2018. Larvicidal activity was determined following the protocol of the World Health Organization (2005). Steam distillation of essential oil from the seeds of N. sativa gave a blackish-coloured oil with percentage yield of 0.54% while that of P. undulata whole plant provided a yellow-coloured oil with a yield of 0.7 %. Results of TLC screening showed the presence of terpenes in the two oils. Ten compounds was identified by the GC/MS in N. sativa seed essential oil. The fatty acid derivative methyl linoleate (18.84%) was the major compound. The GC/MS profile of P. undulata oil revealed the presence of 27 components with the oxygenated monoterpenes (+) carvontanacetone (65.75%) as the main constituent of the oil. Results of the larvicidal activity, after 24h of exposure by each oil, was concentration dependent where the highest percentage mortality (100%) was observed at highest concentration used. Essential oil of N. sativa exhibited larvicidal activity with LC50 = 31.514 and LC90 = 107.128 ppm towards An. gambiae and LC50 = 32.999 and LC90 = 111.381 ppm against Cx. quinquefasciatus. Essential oil from P. undulate whole plant exerted larvicidal activity with LC50 = 33.231 and LC90 = 149.480 ppm against An. gambiae and LC50 = 36.106 and LC90 = viii 144.141 ppm against Cx. quinquefasciatus. These results supported the use of essential oils from plants in insect control as an alternative method for minimizing the noxious effect of some pesticide compounds on the environment. Further investigations including isolation and characterization of bioactive compounds and investigation in depth their mode of action are warranted
  • Item
    Association of Adipokines Levels and Single Nucleotide gene Polymorphisms with Type 2 Diabetes Mellitus among Sudanese patients
    (University of Khartoum, 2021) Halima Babikir Eltahir Abd Allah
    Abstract Background: Type 2 Diabetes Mellitus is characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin resistance. Type 2 DM is a polygenic disorder resulting from a complex interaction between multiple genes and environmental factors. Adiponectin and leptin are adipokines produced by adipocyte, have been linked to the development of type 2 diabetes. Low levels of adiponectin and high levels of leptin have been reported to be associated with insulin resistance and type 2 DM. Several adiponectin and leptin genes polymorphisms are potentially related to the pathophysiology of type 2 DM. This study investigated the association of adiponectin and leptin levels and their single nucleotide polymorphisms with type 2 diabetes mellitus among Sudanese patients. Methods: This was a case control study. Patients with type 2 diabetes202 and 100 non-diabetic controls participated after signing informed written consent. Systolic and diastolic blood pressures were measured (mm Hg), Weight (kg) and height (m) were measured then the body mass index (kg/m2) was determined. Blood samples were collected after an overnight fast. FBG, HbA1c and lipid profiles were measured using enzymatic methods. Adiponectin and leptin were measured using sandwich ELISA. Genotyping for two SNPs of the adiponectin (+276G>T) and leptin(C-2549 A) genes was performed by polymerase chain reaction – restriction fragment length polymorphism (PCR - RFLP.) Results: Patients showed significantly higher Systolic and diastolic blood pressure, BMI, FBG, HbA1c levels, total cholesterol and LDL levels compared with the healthy controls and had significantly lower HDL levels compared with the controls (P <0.05) . Adiponectin level was significantly lower in patients with type 2 diabetes compared with the healthy controls (p<0.001), and it was inversely correlated with HbA1c (Pearson Correlation - 0.197), total cholesterol (r = - 0.139), and LDL (r = - 0.161), and direct correlated with HDL (r= 0.157) P <0.05, there was no correlation with TG level. Leptin level was significantly higher in patients with type 2 diabetes compared with the healthy controls (p<0.05) and it was positively correlated with HbA1c (r= 0.139), total cholesterol (Pearson Correlation .138), and LDL (r= 0 .157) p<0.05. There were no correlation with HDL and TG levels. There were a significant difference in genotypes distribution of SNP (+276G>T), when comparing Type 2 DM patients with healthy control (P <0.05). The T allele and TT / GT / GT+TT) genotypes occurred more frequently than the G allele and GG genotype in Type 2 DM patients. T allele (OR=1.65, 95% CI: 1.184 -2.299, P=0.002), TT (OR=1.32, 95%CI: 0.511 – 3.270, P=0.002), GT (OR =1.82, 95%CIs: 1.24 –2.66 P=0.002), GT+TT (ORs =1.77, 95%CIs: 1.24 – 2.38, <0.001), and associated with a low serum adiponectin levels compared with the GG genotype (P <0.001). Type2DM patients had no significant difference in genotypes distribution of the AA / AC/ CC genotype of leptin gene and A allele frequency compared with the control group (P >0.05) and not associated with leptin level among patients with Type2DM. Conclusion: Patients with type 2 diabetes mellitus had decreased levels of serum adiponectin, high levels of serum leptin. There were significant correlations found between adiponectin and leptin levels with biochemical variables for glycemic control and metabolic dyslipidemia. SNP +276 G/T of the adiponectin gene was associated with low adiponectin levels among patients while leptin SNP C-2549 A was not associated with leptin level among patients with Type2DM in Sudanese population. المستخلص خلفية: يتميز النوع الثاني من داء السكري بارتفاع سكر الدم الناتج عن عيوب في إفراز الأنسولين و / أو مقاومة الأنسولين. داء السكري من النوع الثاني هو اضطراب متعدد الجينات ناتج عن التفاعل المعقد بين الجينات المتعددة والعوامل البيئية. الاديبونكتين واللبتين هما اديبوكاين تنتجهما الخلايا الدهنية, قد تم ربطهما بتطور مرض السكري من النوع الثاني. ارتفاع مستويات الاديبونكتين وانخفاض مستويات اللبتين ذات ارتباط بمقاومة الانسلين ومرض السكري من النوع الثاني . من المحتمل أن ترتبط العديد من الأشكال المتعددة لجينات الأديبونكتين واللبتين بالفيزيولوجيا المرضية لمرض السكري من النوع 2. هدفت هذه الدراسة إلى التحقق من ارتباط مستويات الأديبونكتين واللبتين وتعدد أشكال النيكلوتيدات المفردة لجيناتها مع داء السكري من النوع الثاني بين المرضى السودانيين. طرق البحث : دراسة حالة. شارك في الدراسة 202 مريض السكري من النوع الثاني و 100 فرد اصحاء كمجموعة ضابطة بعد التوقيع على موافقة خطية للمشاركة. تم قياس ضغط الدم الانقباضي والانبساطي(ملم زئبقي), قياس الوزن (كجم) والطول (متر) ثم تم تحديد مؤشر كتلة الجسم(كجم /م2). تم جمع عينات الدم من كلا المجموعتين بعد الصيام طوال الليل ثم تم قياس سكر الدم في فترة الصيام, الهمقلوبين السكري, مستويات الدهون باستخدام الطرق الأنزيمية. تم قياس مستويات الأديبونكتين واللبتين في مصل الدم باستخدام تقنية الممتزالمناعي المرتبط بالانزيم ( الالايزا). تم التعرف علي التنميط الجيني للاشكال المتعددة للنيكلوتيدات المفردة لجينات الأديبونكتين(+276G>T ) واللبتين (C-2549 A ) يإجراء تفاعل البلمرة المتسلسل - تعدد أشكال طول جزء التقييد .(PCR – RFLP) : النتائج كان لدى المرضى ارتفاع ذو دلالة احصائية في ضغط الدم الانقباضي والانبساطي ، مؤشر كتلة الجسم ، الهموقلوبين السكري , الكوليسترول الكلي و الدهون منخضة الكثافة مقارنة بالمجموعة الضابطة, وانخفاض في الدهون عالية الكثافة مقارنة بالمجموعة الضابطة, القيمة الاحتمالية ( P <0.05). كان مستوى الأديبونكتين منخفض بشكل ملحوظ ذو دلالة احصائية في مرضى السكري من النوع 2 مقارنة بالمجموعة الضابطة القيمة الاحتمالية (p<0.001), ومرتبط سلبيا بمستويات الهموقلوبين السكري ( معامل ارتباط بيرسون = 0.197- ) , الكوليسترول الكلي ( ر= - 0.139 ) و الدهون منخضة الكثافة( ر= 0.161- ) ومرتبط ايجابيا بمستوى الدهون عالية الكثافة ( ر= 0.157 ), لايوجد ارتباط بمستوي الجلسريدات الثلاثية. كان مستوى اللبتين اعلى بشكل ملحوظ ذو دلالة احصائية في مرضى السكري من النوع 2 مقارنة بالمجموعة الضابطة القيمة الاحتمالية (p<0.05), ومرتبط ايجابيا بمستويات الهموقلوبين السكري ( ر= 0.139 ) , الكوليسترول الكلي ( ر= 0.138 ) و الدهون منخضة الكثافة( ر= 0.157 ) , لايوجد ارتباط بمستويات الدهون عالية الكثافة و الجلسريدات الثلاثية. اظهرت الدراسة اختلافات ذات دلالة احصائىة في توزيع الأنماط الجينية للاشكال المتعددة للنيكلوتيدات المفردة (+276G>T) لدى مرضى السكري من النوع 2 مقارنة بالمجموعة الضابطة القيمة الاحتمالية (p<0.05), الاليل T والانماط الجينية (TT / GT / GT+TT ) تكررت كثيرا فى مرضى السكري من النوع 2 مقارنة بالاليل G والنمط الجيني ( GG), الاليل T (OR=1.65-95% CI= 1.184 -2.299, P=0.002), النمط الجيني TT (OR=1.32, 95%CI: 0.511 – 3.270, P=0.002), النمط الجيني GT (OR =1.82, 95%CIs: 1.24 –2.66 P=0.002) الانماط الجينية GT+TT (ORs =1.77, 95%CIs: 1.24 – 2.38, <0.001), هذه الانماط الجينية مرتبطة بانخاض مستويات الأديبونكتين في المصل مقارنة بالاليل G والنمط الجيني ( GG) القيمة الاحتمالية (p<0. 001). ليس هناك اختلافات ذات دلالة احصائىة في توزيع الأنماط الجينية (AA / AC/ CC) والاليل A للاشكال المتعددة للنيكلوتيدات المفردة لدي اللبتين(C-2549 A) (AA / AC/ CC) والاليل A لدى مرضى السكري من النوع 2 مقارنة بالمجموعة الضابطة القيمة الاحتمالية ((P >0.05 وغير مرتبطة بمستويات اللبتين في المصل لدى مرضى السكري من النوع 2. الخلاصة: المرضى الذين يعانون من داء السكري من النوع 2 لديهم مستويات منخفضة من الاديبونيكتين ومستويات عالية من اللبتين في مصل الدم. هناك ارتباط ذو دلالة احصائية بين مستويات الأديبونكتين واللبتين مع المتغيرات البيوكيميائية للتحكم في نسبة السكر في الدم واضطراب الدهون. الاشكال المتعددة للنيكلوتيدات المفردة لجين الاديبونكتين(+276G>T ) ترتبط بانخاض مستويات الاديبونكتين لدى مرضى السكري من النوع 2 , بينما لم يكن هناك ارتباط بين الاشكال المتعددة للنيكلوتيدات المفردة وانخاض بمستويات اللبتين لدى مرضى السكري من النوع 2 في السودانيين لجين اللبتين (C-2549 A ).
  • Item
    Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms and Serum Levels of Asymmetric Dimethylarginine with Essential Hypertensionin Sudanese Patients
    (University of Khartoum, ) Sahar Siddig Abdelrahman Gamil ; Abdelrahim Osman Mohamed ; Medical Biochemistry
    Background: Nitric oxide (NO) is important for the anatomical and functional integrity of the vascular endothelium and is produced in endothelial cells by the enzyme endothelial nitric oxide synthase (eNOS) from the amino acid L-arginine. NOS3 gene represents an interesting candidate gene to study the development of Essential hypertension (EH). Asymmetric dimethylarginine (ADMA) is an analogue to arginine and acts as a competitive inhibitor of eNOS. In contrast, symmetric dimethylarginine (SDMA) has no direct effect on eNOS, but plays an important role competing with arginine for transport across the amino acid transporter. ADMA and SDMA have been found to play central roles in the development of EH.Studies done worldwide have found significant association between NOS3 gene polymorphisms and ADMA levels with EH. The new knowledge about NOS3 polymorphisms and ADMA and their role in hypertension have received no attention in Sudan and no previous studies have been done in this respect. The objectives of the study: To assess the relation between three polymorphisms in the NOS3 gene (rs1799983, intron 4 VNTR, and rs2070744) and EH in Sudanese patients. Also to assess the relationshipbetween serum levels of ADMA, SDMA and arginine with EH. Other biochemical characteristics of EH were also investigated. Materials and Methods: Patients (n = 260) > 18 years of age with established hypertension from various health centers and hospitals in Khartoum, and controls (n = 144) > 18 years of age and with normal blood pressure, were included in this case control study. Demographic and biochemical data were collected including venous blood samples. Genomic DNA was extracted and genotypes were determined using TaqMan and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analyses. Biochemical variables were measured using either high performance liquid chromatography- mass spectrometry (HPLC-MS) or manual routine methods. Genotype and allele frequencies were compared between the two groups by χ² analysis, and differences were expressed as odds ratios with 95% confidence intervals (CIs). All other variables were compared between the two groups using Student’s t-testand Mann-Whitney U tests. ANCOVA was used to analyze the differences in arginine, ADMA and SDMA levels. P values < 0.05 were considered statistically significant. Results: The rs2070744 polymorphism in NOS3 was found to be associated with EH in the Sudanese population considering a dominant inheritance model, as the frequency of TC+CC genotypes in patients was significantly higher than that in control subjects (50.4% vs 39.6%, respectively; P = 0.04), with an odds ratio (95% CI) of 0.639 (0.420–0.973). The TT genotype of rs1799983 was associated with elevated diastolic blood pressure (P = 0.01), and the bb genotype of the intron 4 VNTR was found to be associated with smoking (P = 0.034). In addition, the presence of the c allele of the intron 4 VNTR was identified in the Sudanese population. Neither rs1799983 nor the VNTR were associated with EH. Serum arginine levels were significantly lower in patients with EH than in the control group (P< 0.001), while ADMA levels were significantly higher in the hypertensive group (P = 0.002). The difference of SDMA levels between the two groups was insignificant (p=0.152). Patients with EH had significantly higher RBG, TAG, cholesterol, LDL, and CRP levels (all P < 0.001). HDL was significantly lower in the patient group (P< 0.001). Conclusion:The results of this study indicated that the rs2070744 polymorphism in NOS3could be a genetic susceptibility factor for EH in the Sudanese population. This study demonstrated a positive association between ADMA and EH in Sudanese patients. Serum ADMA levels may serve as a future diagnostic marker and a target of therapy in hypertensive patients in Sudan.
  • Item
    Discovery of New Xanthones as Acetylcholine Esterase Inhibitors for Alzheimer’s Disease: In silico and In vitro Approach
    (University of Khartoum, 2015-11-11) Alawi, Mohammed Saeed Hamid ; Magdi Awadalla Mohamed Elhussein, ; Department of Pharmaceutical Chemistry.
    Background: The emergence of peripheral side effects of currently available Acetylcholine Esterase Inhibitors (AChEIs) has called for the discovery of new leads targeting Alzheimer’s disease (AD). Nowadays, in silico methods have been widely accepted as fast tools for lead discovery. The aim of the study is to discover new AChEI lead for AD using In silico and in vitro methods. Methodology: For the first time, more than 8000 compounds, belonging to seven different chemical classes, were virtually screened, using SYBYL package, for their affinities towards AChE. Accessible molecules that showed higher affinities, judged by binding energies, were promoted to the next step. Eight xanthones were docked against 3D structure of AChE using Auto-Dock tools. The in silico revealed enzyme inhibition was further confirmed through in vitro assay following Ellman’s method. The potential enzyme inhibition was assessed using 0.05 M methanolic solution of tested xanthones. Finally, IC50 values were determined using EZ-fit software, statistically analyzed and discussed. Results: All tested xanthones exhibited promising binding energies (− 12.32 to – 8.00 Kcal/mol) with xanthone 7 being the best. The very low binding energy of xanthone 7 was attributed to its higher affinity to AChE. Xanthone 7 binds most of the key residues in esteratic, peripheral anionic, and catalytic anionic sub-sites. The protonated tertiary nitrogen exhibited binding, via pi-cation interactions, with histidine 440 in the esteratic sub-site and phenylalanine 330 and tryptophan 84 in the catalytic anionic sub-site. Furthermore, the peripheral anionic key residues tryptophan 279, tyrosine 70 and tyrosine 334 showed potential interaction with phenyl C−H of 7 via hydrophobic contact. These in silico findings agreed with the in vitro study where xanthone 7 showed the highest AChE inhibitory activity with IC50 = 0.2 µM. Furthermore, the calculated Log P of xanthone 7 was found to be 6.56 revealing its potential CNS penetrability. Conclusion: In silico and in vitro-guided study has resulted in discovery of xanthone 7 which is a new AChEI lead that is herein proposed to enter the development stage of AD new management.