Design, synthesis and anticancer activity of fluorocyclopentenyl-purines and – pyrimidines

Yoon, Ji-seong,Jarhad, Dnyandev B.,Kim, Gyudong,Nayak, Akshata,Zhao, Long Xuan,Yu, Jinha,Kim, Hong-Rae,Lee, Ji Yun,Mulamoottil, Varughese A.,Chandra, Girish,Byun, Woong Sub,Lee, Sang Kook,Kim, Yong-Ch Elsevier 2018 European journal of medicinal chemistry Vol.155 No.-

<P><B>Abstract</B></P> <P>Based on the potent anticancer activity of 6′-fluorocyclopentenyl-cytosine <B>2b</B> in phase IIa clinical trials for the treatment of gemcitabine-resistant pancreatic cancer, we carried out a systematic structure-activity relationship study of 6′-fluorocyclopentenyl-pyrimidines <B>3a</B>-<B>i</B> and -purines <B>3j</B>-<B>o</B> to discover novel anticancer agents. We also synthesized the phosphoramidate prodrug <B>3p</B> of adenine derivative <B>1b</B> to determine if the anticancer activity depended on the inhibition of DNA and/or RNA polymerase in cancer cells and/or on the inhibition of <I>S</I>-adenosylhomocysteine (SAH) hydrolase. All of the synthesized pyrimidine nucleosides exhibited much less potent anticancer activity <I>in vitro</I> than the cytosine derivative <B>2b</B>, acting as RNA and/or DNA polymerase inhibitor, indicating that they could not be efficiently converted to their triphosphates for anticancer activity. Among all the synthesized purine nucleosides, adenine derivative <B>1b</B> and <I>N</I> <SUP>6</SUP>-methyladenine derivative <B>3k</B> showed potent anticancer activity, showing equipotent inhibitory activity as the positive control, neplanocin A (<B>1a</B>) or Ara-C. However, the phosphoramidate prodrug <B>3p</B> showed less anticancer activity than <B>1b</B>, indicating that it did not act as a RNA and/or DNA polymerase inhibitor like <B>2b</B>. This result also demonstrates that the anticancer activity of <B>1b</B> largely depends on the inhibition of histone methyltransferase, resulting from strong inhibition of SAH hydrolase. The deamination of the <I>N</I> <SUP>6</SUP>-amino group, the addition of the bulky alkyl group at the <I>N</I> <SUP>6</SUP>-amino group, or the introduction of the amino group at the C2 position almost abolished the anticancer activity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Eighteen 6′-fluorocyclopentenyl-pyrimidines and -purines were designed and synthesized. </LI> <LI> The mechanism of action of the cytosine analog <B>2b</B> is related to the inhibition of DNA/RNA polymerase. </LI> <LI> The mechanism of action of the adenosine analogs, <B>1b</B> and <B>3k</B> is related to the inhibition of SAH hydrolase. </LI> <LI> The inhibition of SAH hydrolase is associated with the inhibition of histone methyltransferase. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Multiple renal veins clogging the hilum of the right kidney

Satheesha B Nayak(Satheesha B Nayak ),Narendra Pamidi(Narendra Pamidi ),Vasanthakumar Packirisamy(Vasanthakumar Packirisamy ),Soumya Kodimajalu Vasudeva(Soumya Kodimajalu Vasudeva ) 대한해부학회 2023 Anatomy & Cell Biology Vol.56 No.1

Knowledge of variations of renal vessels is of utmost importance in retroperitoneal surgeries and kidney transplant surgeries. We report concurrent variations of the right renal vessels, observed in an adult male cadaver during dissection classes. The right kidney was supplied by three renal arteries, out of which two entered the kidney through the hilum and the other one entered through the lower pole of the kidney. There were five renal veins, emerging independently from the hilum and opening separately through five openings into the inferior vena cava. Among the veins, only one emerged anterior to the renal pelvis and the other four emerged behind it. Four of them terminated into the posterolateral aspect of the inferior vena cava, whereas one terminated into its anterior aspect. Fourth vein from above, received the right testicular vein. The renal hilum was clogged with the presence of seven vessels and renal pelvis.

Fluorocyclopentenyl-cytosine with Broad Spectrum and Potent Antitumor Activity^†

Choi, Won Jun,Chung, Hwa-Jin,Chandra, Girish,Alexander, Varughese,Zhao, Long Xuan,Lee, Hyuk Woo,Nayak, Akshata,Majik, Mahesh S.,Kim, Hea Ok,Kim, Jin-Hee,Lee, Young B.,Ahn, Chang H.,Lee, Sang Kook,Jeon American Chemical Society 2012 Journal of medicinal chemistry Vol.55 No.9

<P>On the basis of the potent biological activity of cyclopentenyl-pyrimidines, fluorocyclopentenyl-pyrimidines were designed and synthesized from <SMALL>d</SMALL>-ribose. Among these, the cytosine derivative <B>5a</B> showed highly potent antigrowth effects in a broad range of tumor cell lines and very potent antitumor activity in a nude mouse tumor xenograft model implanted with A549 human lung cancer cells. However, its 2′-deoxycytidine derivative <B>5b</B> did not show any antigrowth effects, indicating that 2′-hydroxyl group is essential for the biological activity.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jmcmar/2012/jmcmar.2012.55.issue-9/jm3004009/production/images/medium/jm-2012-004009_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jm3004009'>ACS Electronic Supporting Info</A></P>

Investigation of the Wound Healing Activity of Carapa guianensis L. (Meliaceae) Bark Extract in Rats Using Excision, Incision, and Dead Space Wound Models

B. Shivananda Nayak,Joel Kanhai,David M. Milne,William H. Swanston,Shabana Mayers,Mathew Eversley,A.V. Chalapathi Rao 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.5

The objective of our study is to investigate the wound healing activity of the bark extract of Carapa guianensis in rats using three different wound models. The animals were randomly divided into two groups of six each in all the models. Test group animals were treated topically with the bark extract (200mg/kg of body weight), and the controls were treated with petroleum jelly in the excision wound model. In the incision and dead space wound models the test group animals were treated with the extract of C. guianensis (200mg/kg/day) orally by mixing in drinking water, and the control group animals were maintained with plain drinking water. Healing was assessed by the rate of wound contraction, period of epithelialization, skin breaking strength, granulation tissue weight, and hydoxyproline content. Antimicrobial activities of the extract against the microorganisms were also assessed. On day 15 extract-treated animals exhibited 99% reduction in the wound area compared to controls (93%). The extract-treated wounds were found to epithelialize faster than controls (P<.02). The skin breaking strength was significantly higher in extract-treated animals compared to controls (P<.001). The weight and hydroxyproline content of granulation tissue were significantly increased compared to controls. These observations support the use of C. guianensis is in the management of wound healing.

Formation of metastable phases and nanocomposite structures in rapidly solidified Al–Fe alloys

Nayak, S.S.,Chang, H.J.,Kim, D.H.,Pabi, S.K.,Murty, B.S. Elsevier 2011 Materials science & engineering. properties, micro Vol.528 No.18

<P><B>Highlights</B></P><P>► Structures of nanocomposites in rapidly solidified Al–Fe alloys were investigated. ► Nanoquasicrystalline, amorphous and intermetallics phases coexist with α-Al. ► Nanoquasicrystalline phase was observed for the first time in the dilute Al alloys. ► Thermodynamic driving force plays dominant role in precipitation of Fe-rich phases. ► High hardness (3.57GPa) was observed for nanocomposite of Al–10Fe alloy.</P> <P><B>Abstract</B></P><P>In the present work the structure and morphology of the phases of nanocomposites formed in rapidly solidified Al–Fe alloys were investigated in details using analytical transmission electron microscopy and X-ray diffraction. Nanoquasicrystalline phases, amorphous phase and intermetallics like Al<SUB>5</SUB>Fe<SUB>2</SUB>, Al<SUB>13</SUB>F<SUB>4</SUB> coexisted with α-Al in nanocomposites of the melt spun alloys. It was seen that the Fe supersaturation in α-Al diminished with the increase in Fe content and wheel speed indicating the dominant role of the thermodynamic driving force in the precipitation of Fe-rich phases. Nanoquasicrystalline phases were observed for the first time in the dilute Al alloys like Al–2.5Fe and Al–5Fe as confirmed by high resolution TEM. High hardness (3.57GPa) was measured in nanocomposite of Al–10Fe alloy, which was attributed to synergistic effect of solid solution strengthening due to high solute content (9.17at.% Fe), dispersion strengthening by high volume fraction of nanoquasicrystalline phase; and Hall–Petch strengthening from finer cell size (20–30nm) of α-Al matrix.</P>

A peculiar liver with surgically and radiologically important variations: a case report

Satheesha B. Nayak,Snigdha Mishra,Bincy M. George,Surekha D. Shetty,Naveen Kumar,Anitha Guru,Srinivasa S. Rao,Ashwini Aithal 대한해부학회 2013 Anatomy & Cell Biology Vol.46 No.1

A peculiar liver was found in an adult male cadaver during a dissection class for undergraduate medical students. Th e quadrate lobe and fi ssure for the ligamentum teres were totally absent. Th us, the cystic notch on the inferior border was very broad and deep, and the fundus and body of the gall bladder popped out through this notch. Th e cystic duct terminated into the right hepatic duct at the porta hepatis instead of terminating into the common hepatic duct. Awareness of variations of the lobes and fi ssures may minimize a misdiagnosis of liver problems. Th e aim of the current study was to alert radiologists and surgeons about possible variations in the external appearance and anomalies of the lobes and fi ssures of the liver.

Double gallbladder completely enclosed in a cystogastric fold of peritoneum

Satheesha B Nayak,Surekha Devadasa Shetty,Sudarshan Surendran,Raghu Jetti,Naveen Kumar,Srinivasa Rao Sirasanagandla 대한해부학회 2014 Anatomy & Cell Biology Vol.47 No.2

Double gallbladder is one of the rare congenital anomalies of the gallbladder. Failure to detect an accessory gallbladder hampers diagnosis and treatment of cholecystitis, which might result in recurrent attacks of cholecystitis. In addition, presence of peritoneal folds extending from the stomach and duodenum to the gallbladder is very rare. Here we report the presence of a double gallbladder enclosed in a cystogastric fold of the peritoneum. During cadaveric dissection, we observed a cystogastric peritoneal fold that extended from the lesser curvature of the stomach and the first part of the duodenum to the gallbladder. The left end of the peritoneal fold merged with the lesser omentum. It enclosed two gallbladders: the main gallbladder and a small accessory gallbladder. The accessory gallbladder was a small pouch with its fundus attached to the main gallbladder by fibrous tissue, and its duct opened into the main cystic duct.

Eight prehilar branches of the right renal artery

Satheesha B Nayak,Surekha D Shetty,Swamy Ravindra,Srinivasa Rao Sirasanagandla,Ashwini P Aithal,Jyothsna Patil,Naveen Kumar 대한해부학회 2014 Anatomy & Cell Biology Vol.47 No.3

Imaging technology with its advancement in the field of urology is the boon for the patients who require minimally invasive approaches for various kidney disorders. These approaches require a precise knowledge of the normal and variant anatomy of vessels at the hilum of the kidney. During routine dissections, a variation in the branching pattern of the right renal artery was noted in an adult male cadaver. The right renal artery divided into upper and lower divisions 6cm away from the hilum of the kidney. The upper division gave 4 branches, and the lower division gave two branches. These two branches further bifurcated and gave 2 branches each. Thus, there were 8 prehilar branches of renal artery. The multiple prehilar branches led to a congested atmosphere at the hilum of the kidney. This arterial congestion might result in hindering the blood flow at the renal hilum. Apart from this, it might cause difficulties in diagnostic and therapeutic invasive procedures. Knowledge of this variation is of importance to radiologists and urologists in particular.

Functional and clinical importance of a large sized ostium secundum defect in a middle aged female cadaver: a case report

Satheesha B. Nayak 대한해부학회 2017 Anatomy & Cell Biology Vol.50 No.2

Atrial septal defect (ASD) is one of the common congenital anomalies of the heart in humans. Its complications depend on the size of the defect and can manifest at any age. The common symptoms of ASD include dyspnea and fatigue. Most of the ASDs are associated with morbidity and mortality, Earlier the treatment, it is better to the patient. I saw a large ostium secundum defect in the heart of an adult female cadaver during dissection classes for undergraduate medical students. The interatrial septum had large defect at the region where fossa ovalis should have been located. It was about 1.25 inches in diameter and oval in shape. This type of large septal defect might result in cyanosis, stroke or death of the patient at any age.

Sessile ileum, subhepatic cecum, and uncinate appendix that might lead to a diagnostic dilemma

Satheesha B. Nayak,Bincy Muthukattu George,Snigdha Mishra,Sudarshan Surendran,Prakashchandra Shetty,Surekha Devadasa Shetty 대한해부학회 2013 Anatomy & Cell Biology Vol.46 No.4

The subhepatic position of the cecum and appendix is a result of embryological reasons. Subhepatic appendicitis can cause diagnostic dilemmas. During the dissection of an adult male cadaver aged approximately 70 years, the subhepatic position of the cecum and appendix was noted. The appendix made a "U"-shaped bend and its tip was located in the paracolic position. The cecum had appendices epiploicae, and the terminal part of the ileum was retroperitoneal and had ascended vertically to the cecum from the right iliac fossa. Functionally, the sessile part of the ileum might restrict its peristaltic movements. The abnormal position of the terminal ileum might be mistaken for an ascending colon during laparoscopic surgery. The subhepatic position of the cecum and appendix might cause confusion in the diagnosis of acute appendicitis because the tenderness in such cases is not located at the McBurney's point.