Chloro Substitution Research Articles

The Role of Nitro (NO2-), Chloro (Cl), and Fluoro (F) Substitution in the Design of Antileishmanial and Antichagasic Compounds.

Neglected tropical diseases (NTDs) are responsible for over 500,000 deaths annually and are characterized by multiple disabilities. Leishmaniasis and Chagas diseases are among the most severe NTDs, and are caused by the Leishmania sp and Trypanosoma cruzi, respectively. Glucantime, pentamidine, and miltefosine are commonly used to treat leishmaniasis, whereas nifurtimox, benznidazole are current treatments for Chagas disease. However, these treatments are associated with drug resistance and severe side effects. Hence, the development of synthetic products, especially those containing N02, F, or Cl, are known to improve biological activity. The present work summarizes the information on the antileishmanial and antitrypanosomal activity of nitro-, chloro-, and fluorosynthetic derivatives. Scientific publications referring to halogenated derivatives in relation to antileishmanial and antitrypanosomal activities were hand-searched in databases such as SciFinder, Wiley, Science Direct, PubMed, ACS, Springer, Scielo, and so on. According to the literature information, more than 90 compounds were predicted as lead molecules with reference to their IC50/EC50 values in in vitro studies. It is worth mentioning that only active compounds with known cytotoxic effects against mammalian cells were considered in the present study. The observed activity was attributed to the presence of nitro-, fluoro-, and chloro-groups in the compound backbone. All in all, nitro and halogenated derivatives are active antileishmanial and antitrypanosomal compounds and can serve as the baseline for the development of new drugs against leishmaniasis and Chagas disease. However, efforts in in vitro and in vivo toxicity studies of the active synthetic compounds is still needed. Pharmacokinetic studies and the mechanism of action of the promising compounds need to be explored. The use of new catalysts and chemical transformation can afford unexplored halogenated compounds with improved antileishmanial and antitrypanosomal activity.

Albofungin and chloroalbofungin: antibiotic crystals with 2D but not 3D isostructurality.

The potent antibiotics albofungin [systematic name: (1S,4R,8aR)-13-amino-1,15,16-trihydroxy-4-methoxy-12-methyl-3,4,8a,13-tetrahydro-1H-xantheno[4',3',2':4,5][1,3]benzodioxino[7,6-g]isoquinoline-14,17(2H,9H)-dione, C27H24N2O9, 1] and its chlorinated analogue chloroalbofungin (the 11-chloro analogue, C27H23ClN2O9, 2) have been crystallized following their isolation from the bacterial strain Streptomyces chrestomyceticus and their structures determined by single-crystal X-ray diffraction. The novel N-aminoquinolone molecular arrangement shows N-N bond lengths of 1.4202 (16) and 1.424 (2) Å in 1 and 2, respectively. The regiochemistry of chloro substitution in the A-ring is para to the quinolone O atom, with a C-Cl bond length of 1.741 (2) Å. The absolute stereochemistry at three chiral centres of the xanthone rings (i.e. 10S, 13R and 19R) is confirmed. Both compounds crystallize in chiral Sohncke space groups consistent with enantiopurity, but are not fully isostructural. A preserved supramolecular construct (SC) confers two-dimensional (2D) isostructurality, but the SC self-associates via either a twofold screw operation in 1, giving a monoclinic P21 structure, or a twofold rotation in 2, affording a monoclinic C2 structure with a doubled unit-cell axis.

Amino, nitro, chloro, hydroxyl and methyl substitutions may inhibit the binding of PAHs with DNA.

The binding of PAHs with DNA to form PAH-DNA adducts is a crucial step in PAH-induced carcinogenesis. How functional groups affect this binding is largely unknown. Here, we observed that functional group substitutions strongly inhibited PAH-DNA binding. Additionally, -OH substitution has the most potent inhibitory effect as it causes the smallest change in the electrostatic surface potential. Fourier transform infrared spectroscopy and molecular docking analyses demonstrated that PAH derivatives bind with guanine via intercalation and groove binding and then non-specifically insert into the major/minor grooves of DNA. Quantum chemical calculations suggested that hydrogen/halogen bonding may be essential in affecting the binding of functional group-substituted PAHs with DNA. It was further revealed that Log KOA and the PAH derivatives' melting points correlated significantly with binding affinity, implying that changes in the physicochemical characteristics are important factors. This study opens a new window for understanding the relationship between highly toxic PAH derivatives and genetic materials.

In silico fight against novel coronavirus by finding chromone derivatives as inhibitor of coronavirus main proteases enzyme.

Novel coronavirus, 2019-nCoV is a danger to the world and is spreading rapidly. Very little structural information about 2019-nCoV make this situation more difficult for drug designing. Benzylidenechromanones, naturally occurring oxygen heterocyclic compounds, having capability to inhibit various protein and receptors, have been designed here to block mutant variety of coronavirus main protease enzyme (SARC-CoV-2 Mpro) isolated from 2019-nCoV with the assistance of molecular docking, bioinformatics and molecular electrostatic potential. (Z)-3-(4′-chlorobenzylidene)-thiochroman-4-one showed highest binding affinity to the protein. Binding of a compound to this protein actually inhibits the replication and transcription of the virus and, ultimately, stop the virus multiplication. Incorporation of any functional groups to the basic benzylidenechromanones enhances their binding ability. Chloro and bromo substitutions amplify the binding affinity. ADME studies of all these compounds indicate they are lipophilic, high gastro intestine absorbable and blood-brain barrier permeable. The outcome reveals that the investigated benzylidenechromanones can be examined in the case of 2019-nCoV as potent inhibitory drug of SARC-CoV-2 Mpro, for their strong inhibition ability, high reactivity and effective pharmacological properties.Electronic supplementary materialThe online version of this article (10.1007/s11224-020-01537-5) contains supplementary material, which is available to authorized users.

Synthesis and Cytotoxic Evaluation of Novel Benzimidazole Fused Condensed Thienopyrimdines Derivatives

Background: Cancer is a major health problem acting as a global killer and one of the leading causes of death. Most cancer chemotherapeutic drugs currently in clinical use are to kill malignant tumour cells by inhibiting some of the mechanisms implied in cellular division. Thienopyrimidines occupy a special position among the fused pyrimidines, along with other pyrimidines containing an annelated five membered hetero aromatic ring; forms a significant class of drugs which exhibit an array of various biological activities. One of the important current anticancer agent gefitinib acts as tyrosine kinase inhibitors is a quinazoline derivative. The thieno[2,3-d]pyrimidine ring system, is considered as a bioisostere of quinazoline moiety and have attracted great attention due to their broad bioactivities, including antitumor. Methods: Novel thienopyrimidine derivatives were synthesized by cyclization of thiophene o-amino esters with lactam salts such as pyrrolidin-2-one, piperidin-2-one and caprolactam by treating using phosphorous oxychloride. The next set of compounds thieno[2,3-d]pyrimidin-4(3H)-one were synthesised by Niementowski condensations between 2-aminothiophene carboxylate and formamide under reflux condition, followed by its chlorination in good yield. Microwave Fusion of 4-chlorothieno[2,3-d] pyrimidines with o-phenylenediamine afforded target compounds. The target compounds were tested on MCF-7 and HEK293 cell line. Results: The synthesized thirty compounds structures were established by IR, 1H NMR and Mass spectroscopy. The synthesized compounds were obtained in the good yield ranging from 45-70%. The synthesized compounds were subjected to cytotoxicity studies. Among the twenty compounds only one compound showed moderate activity. One of the compound 2c bearing acetyl group had IC50 48.93 μM. However decrease in the size of the lactam ring from six to five member ring or increase to seven member ring resulted in the loss of activity. The IC50 value of 5a was found to be 70.86μg/ml. The compound 5i have more cytotoxic action among the series. Conclusion: A series of thirty compounds belonging to novel pyyrolo, pyrido and benzimidazole fused thienopyrimidines were synthesized, characterized and were evaluated for their in vitro cytotoxicity. The compounds bearing bulky group such as terbutyl group and chloro substitution had the best activity. In conclusion, these structures seems to have biological properties and further investigation on this group could provide a lead.

Regiospecific Introduction of Halogens on the 2-Aminobiphenyl Subunit Leading to Highly Potent and Selective M3 Muscarinic Acetylcholine Receptor Antagonists and Weak Inverse Agonists.

Muscarinic M3 receptor antagonists and inverse agonists displaying high affinity and subtype selectivity over the antitarget M2 are valuable pharmacological tools and may enable improved treatment of chronic obstructive pulmonary disease (COPD), asthma, or urinary incontinence. On the basis of known M3 antagonists comprising a piperidine or quinuclidine unit attached to a biphenyl carbamate, 5-fluoro substitution was responsible for M3 subtype selectivity over M2, while 3'-chloro substitution substantially increased affinity through a σ-hole interaction. Resultantly, two piperidinyl- and two quinuclidinium-substituted biphenyl carbamates OFH243 (13n), OFH244 (13m), OFH3911 (14n), and OFH3912 (14m) were discovered, which display two-digit picomolar affinities with Ki values from 0.069 to 0.084 nM, as well as high selectivity over the M2 subtype (46- to 68-fold). While weak inverse agonistic properties were determined for the biphenyl carbamates 13m and 13n, neutral antagonism was observed for 14m and 14n and tiotropium under identical assay conditions.

Columnar Propeller‐Like 1,3,5‐Triphenylbenzenes: Probing the Effect of Chlorine on the Suzuki Cross‐Coupling and Liquid Crystalline Properties

Suzuki cross‐couplings either between chlorinated N‐methyliminodiacetic acid (MIDA)‐protected aryl boronates and 1,3,5‐tribromobenzene or between chlorinated aryl bromides and phenyltrisboronic species to star‐shaped 1,3,5‐triphenylbenzenes with different substitution patterns and chloro substituents at the outer phenyl rings were studied. The chlorinated precursors required for the respective reaction were synthesized and characterized. Depending on the used coupling reaction target triphenylbenzenes were isolated in yields between 42 % and 88 %. Their mesomorphic properties were influenced by the substitution pattern and number of peripheral chlorine atoms. Triphenylbenzene with 3,5‐alkoxy substitution and H in para‐position self‐assembled into either columnar hexagonal (Colh) mesophases or a soft crystal. While threefold chloro substitution in meta‐position of the outer phenyl rings led to stable room temperature Colho phases, triphenylbenzenes with threefold para‐chloro or 3,5‐dichloro substitution were non‐mesomorphic. Based on X‐ray diffraction data a helical packing model for the observed phases similar to that of related alkoxy‐substituted triphenylbenzenes was proposed.

Synthesis of Thienyl-Isoxazolines and in vitro Screening for their Antimicrobial Activity

A series of thiophene conjugated isoxazoles were efficiently synthesized using a recyclable heterogeneous catalyst Amberlyst-15 in good yields. The synthesized new compounds 5(a-j) were characterized by spectral and elemental analysis and screened in vitro for their antimicrobial potencies. Amongst the synthesized series; compounds 5c and 5j having chloro substitution on both thiophene and aromatic ring exhibited excellent inhibition against the tested species.

Thiazolidin-2-cyanamides derivatives as novel potent Escherichia coli β-glucuronidase inhibitors and their structure–inhibitory activity relationships

Gut microbial β-glucuronidases have the ability to deconjugate glucuronides of some drugs, thus have been considered as an important drug target to alleviate the drug metabolites-induced gastrointestinal toxicity. In this study, thiazolidin-2-cyanamide derivatives containing 5-phenyl-2-furan moiety (1–13) were evaluated for inhibitory activity against Escherichia coli β-glucuronidase (EcGUS). All of them showed more potent inhibition than a commonly used positive control, d-saccharic acid 1,4-lactone, with the IC50 values ranging from 1.2 µM to 23.1 µM. Inhibition kinetics studies indicated that compound 1–3 were competitive type inhibitors for EcGUS. Molecular docking studies were performed and predicted the potential molecular determinants for their potent inhibitory effects towards EcGUS. Structure–inhibitory activity relationship study revealed that chloro substitution on the phenyl moiety was essential for EcGUS inhibition, which would help researchers to design and develop more effective thiazolidin-2-cyanamide type inhibitors against EcGUS.

Lateral substituted phenyl biphenylcarboxylates ‒ non-chiral analogues of ferroelectric liquid crystals

ABSTRACTWe report mesomorphic properties of non-chiral liquid crystalline molecules and study the effect of lateral halogen (fluoro, chloro) substitution in the molecular core and the length of terminal chains. We have prepared nine homologue series with the molecular core substituted at different positions with respect to the ester linkage group. Additionally, we have modified the length of both terminal alkyl chains (hexyl, octyl, decyl and dodecyl) symmetrically for both terminal chains. The effects of the lateral substitution and the chain length are analysed with respect of the possibility to reduce the transition temperatures and tune the properties of presented liquid crystalline molecules.

Evaluation of Pyrano[3,2 C] Quinoline Analogues as Anticancer Agents.

Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. The present study is aimed to evaluate a new series of pyrano[3,2-c]quinoline scaffolds derived from the fusion of bioactive quinolone pharmacophore with structurally diverse aryl substituted chromene for its cytotoxicity. A library of pyrano[3,2-c]quinoline analogues was prepared from one-pot multi component synthesis using various aromatic aldehydes, malononitrile and 2,4-dihydroxy-1-methylquinoline. The new synthetics were primarily screened for its cytotoxicity (IC50) against different human cancer cell lines in vitro. The promising synthetics were further evaluated in vitro for their potency against different kinase activity. The promising compounds were finally tested for their in vivo efficacy in SCID type mice HCT-116 tumor model. The screening results revealed that compounds 4c, 4f, 4i and 4j showed promising activity in in vitro study. However, compound 4c was found to be the most potent candidate with 23% tumor growth inhibition in HCT-116 tumor mice model. The structure activity relationship suggested that 3-substitution on the aryl ring at C4 position of the pyrano[3,2 c]quinolone moiety seems to have an important position for cytotoxicity activity. However, 3- chloro substitution at C4 aryl ring showed a significant alteration of the bioactive conformer of the parent scaffold and outcome with compound 4c as the most potent candidate of the series.

Synthesis of Quaternary Carbon-Centered Benzoindolizidinones via Novel Photoredox-Catalyzed Alkene Aminoarylation: Facile Access to Tylophorine and Analogues

Photoredox-catalyzed aminoarylation and thioamination of unactivated alkenes have been developed, providing novel synthetic routes to access synthetically challenging quaternary carbon-centered ben...

Synthesis of benzotriazoles derivatives and their dual potential as α-amylase and α-glucosidase inhibitors in vitro: Structure-activity relationship, molecular docking, and kinetic studies

Benzotriazoles (4–6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7–40). The synthetic compounds (7–40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α-glucosidase and α-amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC50 values of 2.00–5.6 and 2.04–5.72 μM against α-glucosidase and α-amylase enzymes, respectively. The synthetic compounds were divided into two categories “A” and “B”, in order to understand the structure-activity relationship. Compounds 25 (IC50 = 2.41 ± 1.31 μM), (IC50 = 2.5 ± 1.21 μM), 36 (IC50 = 2.12 ± 1.35 μM), (IC50 = 2.21 ± 1.08 μM), and 37 (IC50 = 2.00 ± 1.22 μM), (IC50 = 2.04 ± 1.4 μM) with chloro substitution/s at aryl ring were found to be most active against α-glucosidase and α-amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α-amylase and non-competitive mode of inhibition against α-glucosidase enzyme.

ROS Inhibitory Activity and Cytotoxicity Evaluation of Benzoyl, Acetyl, Alkyl Ester, and Sulfonate Ester Substituted Coumarin Derivatives.

A number of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, indomethacin, ibuprofen, flufenamic acid, and phenylbutazone are being clinically used to treat inflammatory disorders. These NSAIDs are associated with serious side effects such as gastric ulceration, nephrotoxicity, and bleeding. Therefore, the identification of potent and safe therapy for inflammatory disorders is still of great interest to the medicinal chemist. A series of varyingly substituted benzoyl, acetyl, alkyl ester, and sulfonate ester substituted coumarins 1-64 were screened for the inhibition of ROS, generated from zymosan activated whole blood phagocytes, using luminol-enhanced chemiluminescence technique. Among all tested compounds, 8 (IC50 = 65.0 ± 3.1 μM), 24 (IC50 = 41.8 ± 1.5 μM), 26 (IC50 = 10.6 ± 2.8 μM), 28 (IC50 = 20.9 ± 1.5 μM), and 41 (IC50 = 4.6 ± 0.3 μM) showed good anti- inflammatory potential as compared to standard antiinflammatory drug ibuprofen (IC50 = 54.3 ± 1.9 μM). Specifically, compounds 24, 26, 28, and 41 showed superior activity than standard antiinflammatory drug. Furthermore, compounds 12 (IC50 = 219.0 ± 1.4 μM), 14 (IC50 = 216.5 ± 6.2 μM), 16 (IC50 = 187.4 ± 2.2 μM), and 20 (IC50 = 196.2 ± 2.0 μM) showed moderate ROS inhibitory activity. Limited SAR study revealed that the hydroxy-substituted compound showed better ROS inhibition potential in case of 3-benzoyl and 3-ethylester coumarin derivatives. Whereas, chloro substitution was found to be important in case of 3-acetyl coumarin derivatives. Similarly, in case of sulfonate ester, chloro, and nitro groups especially at positions -4 and -3 of ring "R" played vital role in ROS inhibition. Furthermore, cytotoxicity of all active compounds was also checked on NIH-3T3 cell line. Compounds 12, 14, and 20 were found to be non-cytotoxic. Whereas, 8, 16, 24, 26, 28, and 41 were found to be very weak cytotoxic as compared to standard cycloheximide (IC50 = 0.13 ± 0.02 μM). Identified ROS inhibitors offer the possibility of additional modifications that could give rise to lead structures for further research in order to obtain more potent, and safer antiinflammatory agent.

Conformational restriction design of thiophene-biphenyl-DAPY HIV-1 non-nucleoside reverse transcriptase inhibitors

Conformational restriction is a promising strategy in the development of DAPY-type non-nucleoside reverse transcriptase inhibitors (NNRTIs). Herein, eighteen thiophene-biphenyl-DAPY derivatives were designed and synthesized as potent HIV-1 NNRTIs in which halogen and methyl groups were introduced to explore the conformationally constrained effects. Molecular docking and dynamic simulation analysis indicated that substituents on different positions of the biphenyl ring induced different dihedral angles and binding conformations, further explaining their anti-viral activities. The 2′-fluoro and 3′-chloro substitutions could form electrostatic or halogen-bonding interactions with adjacent residues of the RT enzyme. The 2′-methyl group contributed to enlarge the dihedral angle of biphenyl ring and was positioned to a space-filling hydrophobic pocket. Notably, compounds 22 and 23 with two methyl groups exhibited potent biological activity against WT HIV-1-infected MT-4 cells (EC50 = 14 and 17 nM, respectively) and RT enzyme (EC50 = 27 and 42 nM, respectively). In particular, 23 exhibited much lower cytotoxicity (CC50 = 264.19 μM) and higher selectivity index (SI = 18,564) than etravirine. Taken together, a rational conformational model for further design of DAPYs is proposed, providing a new guidance for the development of NNRTIs.

An Interaction of Chloro Substituted Alkoxy Thiourea as Dopant in Carboxymethyl Cellulose (CMC) for Solid Polymer Electrolyte

Alkoxy substituted aryl-thiourea derivatives provide excellent electronic properties due to the present of rigid π-systems within their molecular framework. This study introduces new thiourea derivative with general formula A-ArC(O)NHC(S)NHAr-D which was successfully synthesized with A is noted as aryl group containing chloro (-Cl) substituent ( 1A ), in which acts as electron acceptor, while D represented as –OC n H 2n+1 , the alkoxy chain tail acts as electron donor. Due to its characteristic of D-π-A system, alkoxy thiourea derivatives are applied as dopant in Carboxymethyl Cellulose (CMC) host material in order to form a conductive biopolymer solid polymer electrolyte (SPE) film. The formation of biopolymer-thiourea complex ( 1A-CMC ) has been analyzed through Fourier Transform Infrared (FTIR) spectroscopy and X-ray diffraction (XRD) to determine the interaction between CMC and thiourea derivative in the form of film as well as Electrical Impedance Spectroscopy (EIS) for their ionic conductivity behavior. The highest conductivity at ambient temperature (303K) exhibits 1.44 x 10 -7 S cm -1 for CMC-thiourea complexation featuring chloro substitution ( 1A ). Indeed, biopolymer electrolyte materials featuring thiourea derivative as dopant has great potential to be developed as electrical conductor. Due to these findings, these so-called molecular wires candidate has opened wide possibilities to be applied in many micro-electronic devices in the near future.

Schiff Base Oxime Derivatives Reactivate Chlorpyrifos-induced Acetylcholinesterase Inhibition

Background: The biological effects of organophosphorus (OP) compounds are connected with the irreversible inhibition of acetylcholinesterase (AChE), an important neuromediator acetylcholine (ACh) splitting enzyme in the human body at the synaptic clefts. Due to this inhibition, AChE is unable to fulfil its physiological function resulting in the accumulation of ACh, which, in turn over stimulates the parasympathetic nerve receptors, and causes fatal cholinergic crisis.
 Objective: The objective of the study was to synthesize a series of Schiff base oximes and to assess their evaluating for their in vitro reactivating potency against chlorpyrifos inhibited AChE.
 Methods: The amino group of 4-amino acetophenone exploited by treating with substituted benzaldehyde in the presence of glacial acetic acid to form Schiff base (1a-1f). The titled compounds (2a-2f) were prepared by treating Schiff base with hydroxylamine hydrochloride in the presence of alcohol. Through structural and spectral analysis, the structure of compounds was confirmed. The synthesized compounds were evaluated for their reactivation efficacy against chlorpyrifos-inhibited rat brain AChE by Ellman's method.
 Results: The pralidoxime (2-PAM) was potent reactivation against chlorpyrifos-inhibited AChE at the concentration tested (0.001 M). In this case, the compounds 2a (40.4%, 60 min) and 2d (37.9%, 60 min) showed promising reactivation as compared to 2-PAM (40.6%, 60min) against chlorpyrifos-inhibited AChE.
 Conclusion: Compounds having chloro (2a) and nitro (2d) substitution on 4th position gave good activity against chlorpyrifos-inhibited AChE. Moreover, these Schiff base oximes seem to be very promising because of their sufficient reactivation strength at lower concentration (10-3 M).

Insights into supramolecular assembly formation of diethyl aryl amino methylene malonate (DAM) derivatives assisted via non-covalent interactions

The crystal structures of four derivatives of diethyl 2-(((aryl)amino)methylene)malonate (DAM) have been studied by single crystal X-ray diffraction. The molecular structures of all the four derivatives were found to be in co-planar conformation. The detailed analysis of molecular conformation in four derivatives reveals the presence of a common strong intramolecular N–H⋯O hydrogen bonding, forming a ring of graph-set motif S11 (6). The effect of chloro and nitro substitution on their relative strengths of hydrogen bonding are analyzed here. Particularly, in compound 1, additional intramolecular hydrogen bonding between –NO2 and N–H was observed that results in the formation of another six-membered chelate ring. On the other hand in case of compound 3, we have observed type-I Cl⋯Cl interaction for the first time in this class of compounds. Further, Hirshfeld surface has been generated that is mapped with dnorm shape index and curvedness to summarize the weak interactions and examine the molecular shapes in all four derivatives. Effect of nitro (1 and 2) and chloro (3 and 4) substitution on the C⋯H, N⋯O and C⋯O interaction is highlighted in molecular contour and 2D fingerprint plots.

Synthesis, characterization, crystal structures and biological screening of 4-amino quinazoline sulfonamide derivatives

Three quinazolin-4-ylamino derivatives containing phenylbenzenesulfonamides (7a-7c) were synthesized by reacting (E)-N'-(2-cyanophenyl)-N,N-dimethyl formamidine (6) with different 4-amino-N-(phenyl)benzenesulfonamides (4a-4c) and characterized by different techniques such as HRMS, IR, 1H NMR and 13C NMR spectroscopy. The structural properties were further examined by single crystal X-ray diffraction method. The X-ray data shows that compounds 7a and 7c contain two molecules and 7b contains one molecule in the asymmetric unit. Comparison of conformation of two distinct molecules, “A” and “B”, in the asymmetric unit of 7a and 7c were studied with the aid of reported literature. The in vitro antiproliferative activity of the compounds was tested against two breast cancer cell lines (MDA-MB-231 and MCF7). Compound 7b observed as a highest potent candidate against MDA-MB-231with IC50 of 5.44 μg/mL. Antimicrobial activity was also screened against bacterial and fungal strains. Compound 7a with chloro substitution was observed as the most potent candidate against the Gram-negative bacterial strains, whereas the compounds showed no significant activity against the fungal strain.

Synthesis and Antimicrobial Activity of Piperine Analogues Containing 1,2,4-Triazole Ring

A series 1,2,4-triazole piperine analogues (TP1-TP6) were designed and synthesized. The structures were confirmed using 1H NMR and 13C NMR. Antibacterial study was done using Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative micro-organisms (E. coli and Pseudomonas aeruginosa) by disc diffusion method. Compound containing chloro substitution (TP6) showed the highest effect, while compound TP1, TP3, TP4, TP5 showed the moderate activity.