S. M. Abdur Rahman

BRIDGED NUCLEIC ACIDS: DEVELOPMENT, SYNTHESIS AND PROPERTIES

Restricting the sugar moiety of a nucleic acid to a single conformation can be accomplished by forming a bridge in the sugar. A large number of bridged nucleic acids with variable bridged structures and conformations have been developed. The synthesis and properties of these artificial nucleic acid analogues are discussed. Such conformational restriction of the sugar moiety significantly improved the properties of the nucleic acid.

2',4'-BNA(NC): a novel bridged nucleic acid analogue with excellent hybridizing and nuclease resistance profiles.

Oligonucleotides modified with 2 ′,4 ′-BNA NC (N-H)/(N-Me) monomers exhibited excellent hybridizing and nuclease resistance properties. Duplex and triplex thermal stabilities were greatly enhanced by incorporating 2′,4′-BNA NC (N-H) and (N-Me) monomers and nuclease resistance was tremendously higher than that of natural oligonucleotide.

A model study for the total synthesis of (±)-scopadulin: stereoselective construction of the A/B ring system with desired functionalities

Abstract A model study toward the total synthesis of (±)-scopadulin is described. Stereocontrolled synthesis of the A/B ring system with desired functionalities was achieved by stereoselective cyanation of a bicyclic enone with Et 2 AlCN, diastereoselective construction of a quaternary carbon at C-4 with LDA-BOMCl, and conversion of the cyano group into a methyl group.

Hybridizing ability and nuclease resistance profile of backbone modified cationic phosphorothioate oligonucleotides.

Various stereochemically pure cationic phosphorothioate oligonucleotides bearing aminoalkyl moieties were synthesized, and their duplex-forming ability against single-stranded DNA (ssDNA), single-stranded RNA (ssRNA) and triplex-forming ability against double-stranded DNA (dsDNA) were evaluated by UV melting experiments. The cationic Rp stereoisomers showed improved duplex-forming ability against ssDNA, triplex-forming ability against dsDNA and nuclease stability.

In-vivo anti-inflammatory and anti-pyretic activities of Manilkara zapota leaves in albino Wistar rats

Objective To screen ethanolic extracts of Manilkara zapota leaves (Family: Sapotaceae) and its different solvent soluble fractions for possible anti-inflammatory, anti-pyretic activities in experimental albino Wistar rats.

Transition Metal Complexes of Naproxen: Synthesis, Characterization, Forced Degradation Studies, and Analytical Method Verification

The aim of our current research was to synthesize some transition metal complexes of Naproxen, determine their physical properties, and examine their relative stability under various conditions. Characterizations of these complexes were done by 1H-NMR, Differential Scanning Calorimetry (DSC), FT-IR, HPLC, and scanning electron microscope (SEM). Complexes were subjected to acidic, basic, and aqueous hydrolysis as well as oxidation, reduction, and thermal degradation. Also the reversed phase high-performance liquid chromatography (RP-HPLC) method of Naproxen outlined in USP was verified for the Naproxen-metal complexes, with respect to accuracy, precision, solution stability, robustness, and system suitability. The melting points of the complexes were higher than that of the parent drug molecule suggesting their thermal stability. In forced degradation study, complexes were found more stable than the Naproxen itself in all conditions: acidic, basic, oxidation, and reduction media. All the HPLC verification parameters were found within the acceptable value. Therefore, it can be concluded from the study that the metal complexes of Naproxen can be more stable drug entity and offer better efficacy and longer shelf life than the parent Naproxen.

Interrupted 2′-O,4′-C-Aminomethylene Bridged Nucleic Acid Modification Enhances Pyrimidine Motif Triplex-Forming Ability and Nuclease Resistance Under Physiological Condition

Due to instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex formation-based strategies in vivo, such as regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis. To this end, we investigated the effect of our previously reported chemical modification, 2′-O,4′-C-aminomethylene bridged nucleic acid (2′,4′- BNANC) modification, introduced into interrupted and continuous positions of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at physiological pH. The interrupted 2′,4′-BNANC modifications of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold, and significantly increased the nuclease resistance of TFO. On the other hand, the continuous 2′,4′-BNANC modification of TFO showed lower ability to promote the triplex formation at physiological pH than the interrupted 2′,4′-BNANC modifications of TFO, and did not significantly change the nuclease resistance of TFO. Selection of the interruptedly 2′,4′-BNANC-modified positions in TFO was more favorable for achieving the higher binding affinity of the pyrimidine motif triplex formation at physiological pH and the higher nuclease resistance of TFO than that of the continuously 2′,4′-BNANC-modified positions in TFO. We conclude that the interrupted 2′,4′-BNANC modification of TFO could be a key chemical modification to enhance pyrimidine motif triplex-forming ability and nuclease resistance under physiological condition, and may eventually lead to progress in various triplex formation-based strategies in vivo.

Improved method of an unusual conversion of aliphatic amines into alcohols

Abstract An improved method for the synthesis of alcohols from amines was achieved using a degassed diethylene glycol and KOH. Utilizing this method, facile conversion of a cyano group, even a sterically hindered one, to a hydroxy-methyl group was also accomplished.

Synthesis, Characterization and Comparison of Local Analgesic, Anti-Inflammatory, Anti-Ulcerogenic Activity of Copper and Zinc Complexes of Indomethacin

BACKGROUND Non-steroidal anti-inflammatory drugs (NSAID) exert gastrointestinal upset by inhibiting mucosal cyclooxygenase (COX) activity and complexation technique with metals has been adopted to overcome this drawback. OBJECTIVE The study aimed to overcome the gastrointestinal side effects associated with indomethacin treatment by synthesizing copper (Cu) and zinc (Zn) complexes of indomethacin along with assessing potential pharmacological effects of these complexes. METHOD The characterization of synthesized complexes was done by FT-IR, XRD, UV-Vis, Atomic Absorption Spectroscopy (AAS) and Differential Scanning Calorimetry (DSC). Biological properties as local analgesic activity, anti-inflammatory activity and antiulcerogenic activity were evaluated following radiant heat tail flick, inhibition of rat hind paw edema and inhibition of NSAID induced gastroenteropathy method respectively. RESULTS 0.3 ml of indomethacin-copper complex demonstrated prominent analgesia at 25 µg/ml dose and 0.3 ml of indomethacin-zinc complex, after 30, 60 and 90 minutes of oral administration, shown significant local analgesia at 25, 50 and 100 µg/ml dose. In antiinflammatory activity assay, indomethacin-copper exhibited significant inhibition at 20 mg/kg dose after 2nd, 3rd and 4th hour of administration whereas indomethacin-zinc illustrated significant inhibition at 10 mg/kg dose after 2nd, 3rd and 4th hour of administration. Anti-ulcerogenic activity study of the complexes exhibited no macroscopic damage to the stomach and intestine, except minor microscopic damage. CONCLUSION In view of the results, the copper and zinc complexes of indomethacin may be used as better substitutes of the parent indomethacin owing to their minimal side effects with additional pharmacological effects.

Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice

Abstract Context Manilkara zapota (L.). P. Royen. (Sapotaceae) has been used in folk medicine to treat pain, diarrhoea, inflammation, arthralgia, and other disorders. Objective Screening of Manilkara zapota leaves ethanol extract and its different solvent soluble fractions for possible antinociceptive and antidiarrhoeal activities in Swiss albino mice. Materials and methods The extract and various fractions (200 and 400 mg/kg body weight; p.o.) were tested for peripheral and central antinociceptive activity by acetic acid-induced writhing and radiant heat tail-flick method, respectively; castor oil-induced diarrhoeal model was used to evaluate antidiarrhoeal activity at both doses. All the samples were administered once in a day and the duration of study was approximately 5 h. Results Ethanol extract (400 mg/kg), petroleum ether fraction (400 mg/kg), and ethyl acetate fraction (400 mg/kg) showed significant peripheral antinociceptive activity having 59.89, 58.24, and 46.7% (p < 0.001) of writhing inhibition, respectively, which is comparable with that of standard diclofenac (59.34% inhibition). The ethanol extract (400 mg/kg) and petroleum ether fraction (400 mg/kg) also showed promising central analgesic activity having 74.15 and 82.15% (p < 0.001) elongation of reaction time, respectively, at 90 min after administration of sample which is also similar to that obtained by morphine (85.84% elongation). In antidiarrhoeal activity screening, ethanol extract (200 and 400 mg/kg) showed significant inhibition of defecation by 53.57 and 60.71%, respectively (p < 0.001) compared with that of loperamide (71.42%). Discussion and conclusion The findings of the studies demonstrated antinociceptive and antidiarrhoeal activities of M. zapota leaves which could be the therapeutic option against pain and diarrhoeal disease.