Department of Chemistry
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Item Current pharmacophore based approaches for the development of new anti-Alzheimer’s agents(Elsevier, 2024-11) Shukla, ParitoshAmyloid beta peptide (Aβ) and hyperphosphorylated neuronal tau proteins accumulate in neurofibrillary tangles in Alzheimer’s disease (AD), a chronic neurodegenerative illness. Chronic inflammation in the brain, which promotes disease progression, is another feature of the Alzheimer’s disease pathogenesis. Approximately 60–70 % of dementia cases are caused by AD. The development of effective therapies for the treatment of AD is urgently needed given the severity of the condition and its rapidly rising prevalence. Cholinesterase inhibitors, beta-amyloid (A-beta), tau inhibitors, and many other medications are currently used as preventive medicine for AD. These medications can temporarily suppress dementia symptoms but cannot halt or reverse the disease’s progression. Many international pharmaceutical companies have tried numerous times to develop an amyloid clearing medication based on the amyloid hypothesis, but without success. Therefore, the amyloid theory may not be entirely plausible. This review mainly covers the recent and important reported pharmacophores as the starting point to discuss already known targets like tau, butyrylcholinesterase, amyloid beta, and acetylcholinesterase and covers the literature between years 2019–2024.Item Synthesis of novel multifunctional spirobibenzopyran derivatives: Crystal structure, In-silico study, anticancer activity and antimycobacterial activity(Elsevier, 2025) Shukla, ParitoshA Novel series of multifunctional Spirobibenzopyran derivatives were synthesized from derivatives of 2-hydroxybenzaldehyde and various ketones with α-hydrogen. Single crystal X-ray analysis was obtained for three compounds. The drug-likeliness and toxicity predictions confirmed minimal toxicity (class IV). Docking showed good complementarity of active compounds with the colchicine binding site of tubulin. Molecular docking showed that methoxy group containing compound-7 binds to the proposed target (colchicine active site) with highest docking score. The synthesized molecules were evaluated as potent anticancer agents against MCF-7, MDA-MB-231 (human breast carcinoma) and A549 (human lung carcinoma) cell lines using MTT assay. In general, substituted spirobibenzopyran compounds showed higher activity towards the lung cancer cell line (A549) and breast cancer cell line (MCF-7 and MDA-MB-231) as compared to unsubstituted spirobibenzopyran molecule. They exhibit competitive results with the reference drug Crizotinib and 5-Fluorouracil. Spirobibenzopyran compound-5 with two phenolic hydroxyl group revealed a promising drug profile, inhibiting cell growth and proliferation against lung cancer cell line (A549) with IC50 value 13.54 ± 3.46 µM. Methoxy substituted compound-7 showed best potency among all spirobibenzopyrans against triple negative cell line MDA-MB-231 having IC50 value 18.96 ± 5.77 µM. As per our best knowledge this is the first report of Antimycobacterial activity of spirobibenzopyrans against Mycobacterium smegmatis MC2 155. Compound-6 with polar carboxylic acid functionality showed enhanced Antimycobacterial activity (MIC 5 µg/mL) as compared to standard drug Rifampicin.Item Cyclization of Oxa-Bicyclic Alkenes with β-Iodo-(Z)-propenoates and o-Iodobenzoate Catalyzed by Nickel Complexes: A Simple Efficient Route to Annulated Coumarins(ACS, 2003) Shukla, ParitoshIn the presence of Ni(dppe)Br2 and Zn powder in acetonitrile at 80 °C, oxa-bicyclic olefins undergo cyclization with o-iodobenzoate and with β-iodo-(Z)-propenoates to give the benzocoumarin derivatives in moderate to good yields. This methodology offers a simple efficient way for the synthesis of structurally complicate coumarins in one pot.Item Cobalt-Catalyzed Reductive Coupling of Saturated Alkyl Halides with Activated Alkenes Paritosh Shukla, Yun-Chu Hsu and Chien-Hong Cheng(OCP, 2006) Shukla, ParitoshAn efficient cobalt-catalyzed reductive coupling reaction of alkyl halides with alkenes bearing electron-withdrawing groups in the presence of water and zinc powder in acetonitrile gave the corresponding Michael-type addition products in high yields. The mechanism is discussed.Item Facile β-Alkyl and β-Hydride Elimination in the Nickel-Catalyzed Annulation of o-Iodophenyl Ketones and Aldehydes with Bicyclic Alkenes(ACS, 2006-05-26) Shukla, Paritosho-Iodoaryl aldehydes react with bicyclic alkenes in the presence of NiBr2(dppe) and Zn powder in acetonitrile at 80 °C undergoing annulation to give polycyclic ketone derivatives. Surprisingly, o-iodoaryl alkyl ketones also react with bicyclic alkenes to form polycyclic ketones with structures the same as those from the corresponding o-iodoaryl aldehydes.Item Structure-Based Drug Design of Novel Aurora Kinase A Inhibitors: Structural Basis for Potency and Specificity(ACS, 2009-01-13) Shukla, ParitoshAurora kinases have emerged as attractive targets for the design of anticancer drugs. Through structure-based virtual screening, novel pyrazole hit 8a was identified as Aurora kinase A inhibitor (IC50 = 15.1 μM). X-ray cocrystal structure of 8a in complex with Aurora A protein revealed the C-4 position ethyl carboxylate side chain as a possible modification site for improving the potency. On the basis of this insight, bioisosteric replacement of the ester with amide linkage and changing the ethyl substituent to hydrophobic 3-acetamidophenyl ring led to the identification of 12w with a ∼450-fold improved Aurora kinase A inhibition potency (IC50 = 33 nM), compared to 8a. Compound 12w showed selective inhibition of Aurora A kinase over Aurora B/C, which might be due to the presence of a unique H-bond interaction between the 3-acetamido group and the Aurora A nonconserved Thr217 residue, which in Aurora B/C is Glu and found to sterically clash with the 3-acetamido group in modeling studies.Item Diazapentacene Derivatives as Thin-Film Transistor Materials: Morphology Control in Realizing High-Field-Effect Mobility(ACS, 2009) Shukla, Paritosh5,7,12,14-Tetrachloro-6,13-diaza-6,13-dihydropentacene (TCDAHP) and 5,7,12,14-tetrachloro-6,13-diazapentacene (TCDAP) were synthesized and assessed as the active channel materials for thin-film transistor applications. Analyses of the crystal structures of these molecules revealed that both exhibited slipped π−π stacking of the long and fused aromatic moiety. Although the packing features of the two compounds are basically identical, their highest occupied molecular orbitals, which are relevant to hole transport, are very different. Better mobility was predicted for TCDAHP over TCDAP based on the dimeric structure in the X-ray coordinates. The morphologies of thin films of TCDAHP and TCDAP prepared by thermal evaporation depend critically on the substrate on which the molecules were deposited: from the amorphous state on a SiO2/Si surface to the crystalline state on a pentacene buffer layer surface. The performance of thin-film transistors prepared on various substrate surfaces was studied. While no field-effect mobility was observed for these films deposited on SiO2/Si, a high mobility of 1.4 cm2/(V s) for the TCDAHP film was achieved when deposited on a pentacene buffer layer prepared on a rubbed monolayer of n-nonyltrichlorosilane on a SiO2/Si surface. A similar device prepared from TCDAP gave a mobility of 0.13 cm2/(V s).Item Scaffold-Hopping Strategy: Synthesis and Biological Evaluation of 5,6-Fused Bicyclic Heteroaromatics To Identify Orally Bioavailable Anticancer Agents(ACS, 2011-03-24) Shukla, ParitoshUtilizing a scaffold-hopping drug-design strategy, we sought to identify a backup drug candidate for BPR0L075 (1), an indole-based anticancer agent. For this purpose, 5,6-fused bicyclic heteroaromatic scaffolds were designed and synthesized through shuffling of the nitrogen from the N-1 position or by insertion of one or two nitrogen atoms into the indole core of 1. Among these, 7-azaindole core 12 showed potent in vitro anticancer activity and improved oral bioavailability (F = 35%) compared with 1 (F < 10%).Item Developments and challenges in biodiesel production from microalgae: A review(2015-07-14) Shukla, Paritosh; Mehrotra, Sandhya Amol; Mehrotra, RajeshThe imminent depletion of fossil fuels and the surging global demand for renewable energy have led to the search for nonconventional energy sources. After a few decades of trial and error, the world is now testing the sources of the third generation of fossil fuels, which contain for most parts microalgae. With more than 80% oil content, being adaptable in growth parameters and highly versatile, microalgae are highly promising sources of biofuels in the present time. The present article makes a sweeping attempt to highlight the various methods employed for cultivation of microalgae, techniques to harvest and extract biomass from huge algal cultures, as well as their downstream production and processing procedures. The advantages, limitations, and challenges faced by each of them have been described to some extent. Major concerns pertaining to biofuels are supposed to be their environmental sustainability and economic viability along with their cost effectiveness. This would require a great deal of empirical data on existing systems and a great deal of optimization to generate a more robust one. We have concluded our article with a SWOT analysis of using algae for biodiesel production in a tabulated form.Item Nickel-catalyzed reductive Heck type coupling of saturated alkyl halides with acrylates and oxabenzonorbornadiene(Elsiever, 2015-04-15) Shukla, ParitoshThe Heck reaction is a well-established transition-metal catalyzed reaction for coupling alkenes with sp2 alkyl halides to give novel unsaturated compounds. Herein we report an analogous Heck-inspired, simple efficient coupling of sp3 alkyl halides with electron-withdrawing alkenes to form reductive coupling products where saturated esters are obtained. A range of acrylates were coupled with sp3 alkyl halides in the presence of Ni(PPh3)2Cl2 catalyst, Zn metal powder, CH3CN solvent, and water, at 80 °C to form the reductive Heck type saturated ester products in good yields. This strategy was further extended to couple oxabenzonorbornadiene with the alkyl halides resulting in ring opening to give rise to bicyclic alcohol products. The mechanism for both the reactions appears to be the usual oxidative-addition driven alkene insertion reaction where the water appears to act as the protonating agent.