Nizam Uddin

Identification of bisindolylmethane–hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations

The present study involves the synthesis of bisindolylmethane–hydrazone hybrids, 1–30, in a three-step reaction sequence, followed by evaluation against β-glucuronidase enzyme. The IC50 values for the potent compounds were in the range from 0.10 to 83.50 μM. Compound, a trihydroxy analog was found to be the most potent derivative, having an IC50 value of 0.10 ± 0.001 μM. Molecular docking revealed that the active compounds could fit perfectly into the binding groove of β-D-glucuronidase. The presence of hydroxyl groups on the aromatic side chain proved to be the single most important factor that contributed toward the inhibitory potential of these compounds. On the other hand, the imino group of the hydrazone linkage displayed interactions with the side chain carboxyl oxygen (Oe2) of Asp207. The high inhibitory potential of these compounds could be associated with these strong hydrogen bonds. Structures of all the synthesized compounds were confirmed using modern spectroscopic methods.

Bioassay-guided isolation of urease and α-chymotrypsin inhibitory constituents from the stems of Lawsonia alba Lam. (Henna).

Seven constituents were isolated from the stems of Lawsonia alba Lam., following an activity-guided isolation, which include two new constituents, namely lawsorosemarinol (1) and lawsofructose (2), one known compound 2-(β-d-glucopyranosyloxy)-1, 4-naphthoquinone (3) and four compounds, 4-hydroxy coumarine (4), 3-(4-hyroxyphenyl)-triacontyl-(Z)-propenoate (5), 3-(4-hydroxy-3-methoxyphenyl)-triacontyl-(Z)-propenoate (6) and 7-hydroxy-4-methyl coumarin (7) first time isolated from Lawsonia alba. Their structure elucidation was based on spectroscopic data analyses. Compounds 3 and 7 showed a moderate inhibition of urease activity, while rest of them showed less than 50% inhibition. These compounds did not show any significant inhibition against α-chymotrypsin.

Molecular hybridization conceded exceptionally potent quinolinyl-oxadiazole hybrids through phenyl linked thiosemicarbazide antileishmanial scaffolds: In silico validation and SAR studies

The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover a novel series of compounds 6-23 based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal potential. The most potent compound (23, IC50=0.10±0.001μM) among the series was found ∼70 times more lethal than the standard drug. The current series 6-23 conceded in the development of fourteen (14) extraordinarily active compounds against leishmaniasis. In silico analysis were also performed to probe the mode of action while all the compounds structure were established by NMR and Mass spectral analysis.

Two new dioxin derivatives from the aerial parts of Lawsonia alba

From the aerial parts of Lawsonia alba two new dioxin derivatives, namely 12-[2′-(1′, 4′-dioxin-5′, 6′-dione)-8″E-undecenyl-dodecanoate (1) and 5-[1′-(docosa-2′E, 5′E-dienyl)]-1,4-dioxin-2,3-dione (2), were isolated and characterised on the basis of spectroscopic methods.

Synthesis of 2-phenyl-1H-imidazo[4,5-b]pyridine as type 2 diabetes inhibitors and molecular docking studies

A series of imidazo[4,5-b]pyridines (3–32) was synthesized and evaluated for their ability to inhibit Baker’s yeast α-glucosidase enzyme. The IC50 values for all compounds were in the range of 13.5–93.7 µM with compound 15, a 2,4-dihydroxy-substituted analog, displayed the most potent activity potential. Structure–activity relationship strongly suggested the presence of hydroxyl group at aromatic side chain as the main contributing factor towards the inhibitory potential. Findings also suggested that compounds having hydroxyl groups at ortho and para positions are able to inhibit α-glucosidase enzyme efficiently. This experimental observation was further supported by docking studies carried out on human intestinal maltase-glucoamylase enzyme (PDB ID: 3TOP). The –NH– group of imidazo-pyridine of compound 15 formed H-bond with Asp1526, while both hydroxyls of catechol formed H-bond with Asp1279. Imidazo-pyridine ring was well stabilized by π–π stacking with Phe1560, and other hydrophobic interactions involving side chain of Pro1159, Tyr1167, Asp1157, Met1421, Trp1369, Pro1318, and Lys1460. The catechol ring also forms several hydrophobic interactions with Phe1560, Trp1523, Trp1418, His1584, Try1251, Ile1218 and Trp1355.

New anthrarobin acyl derivatives as butyrylcholinesterase inhibitors: synthesis, in vitro and in silico studies

To treat Alzheimers disease (AD), the available candidates are effective only against mild AD or have side effects. So, a study was planned to synthesis new candidates that may have good potential to treat AD. A series of new anthrarobin acyl derivatives (2–8) were synthesized by the reaction of anthrarobin (1) and acetic anhydride/acyl chlorides. The product were characterized by 1H NMR and EI-MS, and evaluated for butyrylcholinesterase (BuChE) inhibition activity. Compounds 5 and 4 showed notable BuChE inhibitory potential with IC50 5.3 ± 1.23 and 17.2 ± 0.47 μM, respectively when compared with the standard eserine (IC50 7.8 ± 0.27 μM), compound 5 showed potent BuChE inhibition potential than the standard eserine. The active compounds 5 and 4 have acyl groups at 2-OH and 10-OH positions which may be responsible for inhibitory potential as this orientation is absent in other products. In silico studies of 5 and 4 products revealed the high inhibitory potential due to stable binding of ligand with the BuChE active sites with docking energy score −18.8779 kcal/mol and −23.1159 kcal/mol, respectively. Subsequently, compound 5 that have potent BuChE inhibitory activity could be the potential candidate for drug development for Alzheimer’s disease.

Sargassum swartzii extracts ameliorate memory functions by neurochemical modulation in a rat model

Recently, considerable attention has been paid to drug exploration from natural sources for treating memory loss, a major manifestation of various neurodegenerative diseases. Increasing evidences implicate brain serotonin metabolism in learning and memory, supporting the notion that targeting 5-HT (5-hydroxytryptamine) and its receptors would be beneficial in the treatment of cognitive disorders. In the present study, behavioral and neurochemical effects were examined following administration of Sargassum swartzii extracts in albino Wistar rats. Increase in spatial working memory and recognition memory was exhibited by the seaweed-treated rats as compared to controls. Plasma tryptophan, brain 5-HT, and 5-hydroxyindoleacetic acid levels were measured using HPLC–ECD, and a significant increase in brain 5-HT metabolism was observed in the seaweed-treated rats. The increase in memory functions following repeated administration of S. swartzii extracts is suggested to be due to the increased serotonergic neurotransmission in the brain of seaweed-treated rats.

Antidepressant-like deliverables from the sea: evidence on the efficacy of three different brown seaweeds via involvement of monoaminergic system

Brown seaweeds exhibit several health benefits in treating and managing wide array of ailments. In this study, the antidepressant-like effect of methaolic extracts from Sargassum swartzii (SS), Stoechospermum marginatum (SM), and Nizamuddinia zanardinii (NZ) was examined in forced swimming test (FST), in rats. Oral administration of SS, SM, and NZ extract (30–60 mg/kg) exhibited antidepressant-like activity in FST by reducing immobility time as compared to control group, without inducing significant change in ambulatory behavior in open field test. In order to evaluate the involvement of monoaminergic system, rats were pretreated with the inhibitor of brain serotonin stores p-chlorophenylalanin (PCPA), dopamine (SCH23390 and sulpiride), and adrenoceptor (prazosin and propranolol) antagonists. Rats receiving treatment for 28 days were decapitated and brains were analyzed for monoamine levels. It may be concluded that the extracts of SS, SM, and NZ produces antidepressant-like activity via modulation of brain monoaminergic system in a rat model. Antidepressant-like activities of selected brown seaweeds via modulation of monoaminergic system.